Prognostication in Philadelphia Chromosome Negative Myeloproliferative Neoplasms: a Review of the Recent Literature.

PubMed

Zhou, Amy; Afzal, Amber; Oh, Stephen T

2017-10-01

The prognosis for patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is highly variable. All Ph-negative MPNs carry an increased risk for thrombotic complications, bleeding, and leukemic transformation. Several clinical, biological, and molecular prognostic factors have been identified in recent years, which provide important information in guiding management of patients with Ph-negative MPNs. In this review, we critically evaluate the recent published literature and discuss important new developments in clinical and molecular factors that impact survival, disease transformation, and thrombosis in patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Recent studies have identified several clinical factors and non-driver mutations to have prognostic impact on Ph-negative MPNs independent of conventional risk stratification and prognostic models. In polycythemia vera (PV), leukocytosis, abnormal karyotype, phlebotomy requirement on hydroxyurea, increased bone marrow fibrosis, and mutations in ASXL1, SRSF2, and IDH2 were identified as additional adverse prognostic factors. In essential thrombocythemia (ET), JAK2 V617F mutation, splenomegaly, and mutations in SH2B3, SF3B1, U2AF1, TP53, IDH2, and EZH2 were found to be additional negative prognostic factors. Bone marrow fibrosis and mutations in ASXL1, SRSF2, EZH2, and IDH1/2 have been found to be additional prognostic factors in primary myelofibrosis (PMF). CALR mutations appear to be a favorable prognostic factor in PMF, which has not been clearly demonstrated in ET. The prognosis for patients with PV, ET, and PMF is dependent upon the presence or absence of several clinical, biological, and molecular risk factors. The significance of additional risk factors identified in these recent studies will need further validation in prospective studies to determine how they may be best utilized in the management of these disorders.

Acute Kidney Injury Predicts Major Adverse Outcomes in Diabetes: Synergic Impact With Low Glomerular Filtration Rate and Albuminuria.

PubMed

Monseu, Mathilde; Gand, Elise; Saulnier, Pierre-Jean; Ragot, Stéphanie; Piguel, Xavier; Zaoui, Philippe; Rigalleau, Vincent; Marechaud, Richard; Roussel, Ronan; Hadjadj, Samy; Halimi, Jean-Michel

2015-12-01

Subjects with diabetes are prone to the development of cardiovascular and noncardiovascular complications. In separate studies, acute kidney injury (AKI), albuminuria, and low estimated glomerular filtration rate (eGFR) were shown to predict adverse outcomes, but, when considered together, their respective prognostic value is unknown. Patients with type 2 diabetes consecutively recruited in the SURDIAGENE cohort were prospectively followed up for major diabetes-related events, as adjudicated by an independent committee: death (with cause), major cardiovascular events (myocardial infarction, stroke, congestive heart failure, amputation, and arterial revascularization), and renal failure (i.e., sustained doubling of serum creatinine level or end-stage renal disease). Intrahospital AKI occurred in 411 of 1,371 patients during the median follow-up period of 69 months. In multivariate analyses, AKI was significantly associated with cardiovascular and noncardiovascular death, including cancer-related death. In multivariate analyses, AKI was a powerful predictor of major adverse cardiovascular events, heart failure requiring hospitalization, myocardial infarction, stroke, lower-limb amputation or revascularization, and carotid artery revascularization. AKI, eGFR, and albuminuria, even when simultaneously considered in multivariate models, predicted all-cause and cardiovascular deaths. All three renal biomarkers were also prognostic of most adverse outcomes and of the risk of renal failure. AKI, low eGFR, and elevated albuminuria, separately or together, are compelling biomarkers of major adverse outcomes and death in diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

PubMed Central

Wong, Li-Fan; Lee, Jang-Ming

2016-01-01

Esophageal squamous cell carcinoma (ESCC) is a frequently recurrent deadly cancer for which no efficient targeted drug exists. AXL is an adverse prognostic factor in some cancers. Strong clinical evidence to support the prognostic role of AXL in ESCC is lacking. A total of 116 patients diagnosed with operable primary ESCC were enrolled. Both AXL and HER2 expression were detected by immunohistochemistry (IHC) in esophageal tissue and were correlated with the clinical outcome of patients. The efficacy of the AXL targeted drug foretinib was also evaluated in ESCC cells. Expression of AXL was found in about 80 % of ESCC tissue, and was significantly correlated with progression of tumor (P<0.001), increased risk of death (Hazard ratio HR [95 % CI=2.09[1.09-4.04], P=0.028], and distant metastasis (odds ratio OR [95 %CI]=3.96 (1.16-13.60), P=0.029). The adverse clinical impact of AXL was more evident when cumulatively expressed with HER2. In cell model, ESCC cells were more sensitive to AXL inhibitor foretinib than to the HER2 inhibitor lapatinib. Meanwhile, the AXL inhibitor foretinib showed a synergistic effect with HER2 inhibitors and the potential to overcome drug resistance to lapatinib. We thus concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients. PMID:27172793

Risk factors for adverse outcomes in older adults with blunt chest trauma: A systematic review.

PubMed

Sawa, Jake; Green, Robert S; Thoma, Brent; Erdogan, Mete; Davis, Philip J

2017-08-11

The objective of this study was to systematically review the published literature for risk factors associated with adverse outcomes in older adults sustaining blunt chest trauma. EMBASE and MEDLINE were searched from inception until March 2017 for prognostic factors associated with adverse outcomes in older adults sustaining blunt chest trauma using a pre-specified search strategy. References were independently screened for inclusion by two reviewers. Study quality was assessed using the Quality in Prognostic Studies tool. Where appropriate, descriptive statistics were used to evaluate study characteristics and predictors of adverse outcomes. Thirteen cohort studies representing 79,313 patients satisfied our selection criteria. Overall, 26 prognostic factors were examined across studies and were reported for morbidity (8 studies), length of stay (7 studies), mortality (6 studies), and loss of independence (1 study). No studies examined patient quality of life or emergency department recidivism. Prognostic factors associated with morbidity and mortality included age, number of rib fractures, and injury severity score. Although age and rib fractures were found to be associated with adverse outcomes in more than 3 studies, meta-analysis was not performed due to heterogeneity amongst included studies in how these variables were measured. While blunt chest wall trauma in older adults is relatively common, the literature on prognostic factors for adverse outcomes in this patient population remains inadequate due to a paucity of high quality studies and lack of consistent reporting standards.

Prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations.

PubMed

Miyata, Tatsunori; Yamashita, Yo-Ichi; Yamao, Takanobu; Umezaki, Naoki; Tsukamoto, Masayo; Kitano, Yuki; Yamamura, Kensuke; Arima, Kota; Kaida, Takayoshi; Nakagawa, Shigeki; Imai, Katsunori; Hashimoto, Daisuke; Chikamoto, Akira; Ishiko, Takatoshi; Baba, Hideo

2017-06-01

The postoperative complication is one of an indicator of poor prognosis in patients with several gastroenterological cancers after curative operations. We, herein, examined prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations. We retrospectively analyzed 60 patients with intrahepatic cholangiocarcinoma who underwent primary curative operations from June 2002 to February 2016. Prognostic impacts of postoperative complications were analyzed using log-rank test and Cox proportional hazard model. Postoperative complications (Clavien-Dindo classification grade 3 or more) occurred in 13 patients (21.7%). Overall survival of patients without postoperative complications was significantly better than that of patients with postoperative complications (p = 0.025). Postoperative complications are independent prognostic factor of overall survival (hazard ratio 3.02; p = 0.030). In addition, bile duct resection and reconstruction (Odds ratio 59.1; p = 0.002) and hepatitis C virus antibody positive (Odds ratio 7.14; p= 0.022), and lymph node dissection (Odds ratio 6.28; p = 0.040) were independent predictors of postoperative complications. Postoperative complications may be an independent predictor of poorer survival in patients with intrahepatic cholangiocarcinoma after curative operations. Lymph node dissection and bile duct resection and reconstruction were risk factors for postoperative complications, therefore we should pay attentions to perform lymph node dissections, bile duct resection and reconstruction in patients with intrahepatic cholangiocarcinoma.

The prognostic impact of germline 46/1 haplotype of Janus kinase 2 in cytogenetically normal acute myeloid leukemia

PubMed Central

Nahajevszky, Sarolta; Andrikovics, Hajnalka; Batai, Arpad; Adam, Emma; Bors, Andras; Csomor, Judit; Gopcsa, Laszlo; Koszarska, Magdalena; Kozma, Andras; Lovas, Nora; Lueff, Sandor; Matrai, Zoltan; Meggyesi, Nora; Sinko, Janos; Sipos, Andrea; Varkonyi, Andrea; Fekete, Sandor; Tordai, Attila; Masszi, Tamas

2011-01-01

Background Prognostic risk stratification according to acquired or inherited genetic alterations has received increasing attention in acute myeloid leukemia in recent years. A germline Janus kinase 2 haplotype designated as the 46/1 haplotype has been reported to be associated with an inherited predisposition to myeloproliferative neoplasms, and also to acute myeloid leukemia with normal karyotype. The aim of this study was to assess the prognostic impact of the 46/1 haplotype on disease characteristics and treatment outcome in acute myeloid leukemia. Design and Methods Janus kinase 2 rs12343867 single nucleotide polymorphism tagging the 46/1 haplotype was genotyped by LightCycler technology applying melting curve analysis with the hybridization probe detection format in 176 patients with acute myeloid leukemia under 60 years diagnosed consecutively and treated with curative intent. Results The morphological subtype of acute myeloid leukemia with maturation was less frequent among 46/1 carriers than among non-carriers (5.6% versus 17.2%, P=0.018, cytogenetically normal subgroup: 4.3% versus 20.6%, P=0.031), while the morphological distribution shifted towards the myelomonocytoid form in 46/1 haplotype carriers (28.1% versus 14.9%, P=0.044, cytogenetically normal subgroup: 34.0% versus 11.8%, P=0.035). In cytogenetically normal cases of acute myeloid leukemia, the 46/1 carriers had a considerably lower remission rate (78.7% versus 94.1%, P=0.064) and more deaths in remission or in aplasia caused by infections (46.8% versus 23.5%, P=0.038), resulting in the 46/1 carriers having shorter disease-free survival and overall survival compared to the 46/1 non-carriers. In multivariate analysis, the 46/1 haplotype was an independent adverse prognostic factor for disease-free survival (P=0.024) and overall survival (P=0.024) in patients with a normal karyotype. Janus kinase 2 46/1 haplotype had no impact on prognosis in the subgroup with abnormal karyotype. Conclusions Janus

An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.

PubMed

Chronowski, Gregory M; Wilder, Richard B; Tucker, Susan L; Ha, Chul S; Sarris, Andreas H; Hagemeister, Fredrick B; Barista, Ibrahim; Hess, Mark A; Cabanillas, Fernando; Cox, James D

2002-12-15

The relative importance of prognostic factors in patients with early-stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy. From 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum beta-2-microglobulin (beta-2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum beta-2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94). Follow-up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum beta-2M level was an independent adverse prognostic factor for overall survival (P = 0.0009). The prognostic significance of a simple, widely available, and inexpensive blood test, beta-2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10998

The prognostic impact of worsening renal function in Japanese patients undergoing percutaneous coronary intervention with acute coronary syndrome.

PubMed

Murata, Nobuhiro; Kaneko, Hidehiro; Yajima, Junji; Oikawa, Yuji; Oshima, Toru; Tanaka, Shingo; Kano, Hiroto; Matsuno, Shunsuke; Suzuki, Shinya; Kato, Yuko; Otsuka, Takayuki; Uejima, Tokuhisa; Nagashima, Kazuyuki; Kirigaya, Hajime; Sagara, Koichi; Sawada, Hitoshi; Aizawa, Tadanori; Yamashita, Takeshi

2015-10-01

The prognostic impact of worsening renal function (WRF) in acute coronary syndrome (ACS) patients is not fully understood in Japanese clinical practice, and clinical implication of persistent versus transient WRF in ACS patients is also unclear. With a single hospital-based cohort in the Shinken database 2004-2012 (n=19,994), we followed 604 ACS patients who underwent percutaneous coronary intervention (PCI). WRF was defined as an increase in creatinine during hospitalization of ≥0.3mg/dl above admission value. Persistent WRF was defined as an increase in creatinine during hospitalization of ≥0.3mg/dl above admission value and maintained until discharge, whereas transient WRF was defined as that WRF resolved at hospital discharge. WRF occurred in 78 patients (13%), persistent WRF 35 patients (6%) and transient WRF 43 patients (7%). WRF patients were older and had a higher prevalence of chronic kidney disease, history of myocardial infarction (MI), and ST elevation MI. WRF was associated with elevated inflammatory markers and reduced left ventricular (LV) ejection fraction in acute, chronic phase. Incidence of all-cause death and major adverse cardiac events (MACE: all-cause death, MI, and target lesion revascularization) was significantly higher in patients with WRF. Moreover, in the WRF group, incidences of all-cause death and MACE were higher in patients with persistent WRF than those with transient WRF. A multivariate analysis showed that as well as older age, female gender, and intubation, WRF was an independent determinant of the all-cause death in ACS patients who underwent PCI. In conclusion, WRF might have a prognostic impact among Japanese ACS patients who underwent PCI in association with enhanced inflammatory response and LV remodeling. Persistent WRF might portend increased events, while transient WRF might have association with favorable outcomes compared with persistent WRF. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier

Prognostic and predictive impact of central necrosis and fibrosis in early breast cancer. Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy

PubMed Central

Maiorano, Eugenio; Regan, Meredith M.; Viale, Giuseppe; Mastropasqua, Mauro G.; Colleoni, Marco; Castiglione-Gertsch, Monica; Price, Karen N.; Gelber, Richard D.; Goldhirsch, Aron; Coates, Alan S.

2013-01-01

Purpose A minority of early invasive breast cancers show a pattern of central necrosis and fibrosis (CNF). Previous studies have documented an adverse prognostic impact and association with other adverse pathological features, but its predictive importance for therapy selection is unknown. Methods We examined the prognostic and predictive value of CNF in two randomized clinical trials comparing chemoendocrine therapy with endocrine therapy alone in patients with node-negative breast cancer. A total of 1850 patients randomly assigned to treatment groups comparing endocrine with chemoendocrine therapy, and with centrally-assessed CNF, ER, PgR and HER2 were included in the analytic cohort. The median follow up was 10 years. Results CNF was present in 84 of 1850 trial patients (4.5%). It was associated with tumor characteristics suggesting poor outcome, but was an independent adverse factor for disease-free survival. In the presence of CNF outcome was worse regardless of tumor grade, whereas in the absence of CNF, patients with grade 3 tumors had poorer outcome than those with grade 1-2 tumors. Among patients with estrogen receptor-absent tumors chemoendocrine therapy was superior to endocrine therapy alone only in the absence of CNF [HR (chemoendocrine:endocrine)=0.46 in CNF-absent, 0.90 in CNF-present], while among those with receptor-positive disease chemoendocrine therapy was beneficial only in the presence of CNF [HR=0.34 CNF-present, 0.96 CNF-absent]. Conclusion The results suggest that the presence of CNF reflects a biological difference in early breast cancer that is important in modulating the efficacy of standard therapies. Accordingly we believe that its presence should be routinely reported. PMID:19280340

Prognostic significance of SRSF2 mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia: a meta-analysis.

PubMed

Arbab Jafari, Pourya; Ayatollahi, Hossein; Sadeghi, Ramin; Sheikhi, Maryam; Asghari, Amir

2018-05-14

Serine/arginine-rich splicing factor 2 (SRSF2) mutations were detected frequently in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients. However, its prognostic value has not yet been fully clarified. In this meta-analysis, Hazard Ratio (HR) and 95% confidence interval (CI) for overall-survival (OS) were chosen to evaluate the prognostic impact of SRSF2 mutations and to compare SRSF2 mutations to those with wild-type. A total of 2056 patients from 12 studies were obtained. The pooled HRs for OSsuggested that patients with MDS had a poorer prognosis (HR = 1.780, 95% CI (1.410-2.249)), while analysis on SRSF2 mutations revealed no significant effect on the prognosis of CMML patients (HR = 1.091, 95% CI (0.925-1.286)). The frequency of SRSF2 mutations was found to be 11.5% and 39.8% in patients with MDS and CMML, respectively. This meta-analysis suggests that SRSF2 has a poor prognosis in patients with MDS, but no prognosis impact on patients with CMML. In conclusion, SRSF2 mutations were significantly related to the shorter OS in patients with MDS which may consider as an adverse prognostic risk factor. Whereas, analysis did not show any prognostic effect on OS of CMML patients with SRSF2 mutations.

MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities.

PubMed

Crinière, Emmanuelle; Kaloshi, Gentian; Laigle-Donadey, Florence; Lejeune, Julie; Auger, Nathalie; Benouaich-Amiel, Alexandra; Everhard, Sibille; Mokhtari, Karima; Polivka, Marc; Delattre, Jean-Yves; Hoang-Xuan, Khê; Thillet, Joëlle; Sanson, Marc

2007-06-01

MGMT promoter methylation, which has been correlated with the response to alkylating agents, was investigated in a retrospective series of 219 glioblastomas (GBMs) treated with various modalities. MGMT methylation had no impact on survival for the whole group, but showed a significant advantage (17.1 months vs. 13.1) for patients treated with RT+ adjuvant chemotherapy (relative risk of death (RR) = 0.53; P = 0.041), particularly when patients received CT during the course of RT (MS = 19.9 months vs. 12.5 months; RR = 0.227, P = 0.001). This suggests that the prognostic impact of MGMT methylation is dependent on therapeutic modalities and schedules. MGMT methylation was not correlated with the main molecular alterations, such as 10q loss and p53 expression.

Prognostic significance of interventricular septal thickness in patients with AL amyloidosis.

PubMed

Cho, Hyunsoo; Kim, Soo-Jeong; Shim, Chi Young; Hong, Geu-Ru; Ha, Jong-Won; Kim, Yu Ri; Yang, Woo Ick; Chung, Haerim; Jang, Ji Eun; Cheong, June-Won; Min, Yoo Hong; Kim, Jin Seok

2017-09-01

The major prognostic determinant of immunoglobulin light chain (AL) amyloidosis is cardiac involvement. However, the role of interventricular septal thickness (IVST), which reflects the extent of cardiac involvement, remains unclear. Therefore, we analyzed 77 patients with newly diagnosed AL amyloidosis and evaluated the prognostic role of IVST. Fifty patients (64.9%) had cardiac involvement and 17 patients (22.1%) showed IVST >15mm. Among all patients, the revised Mayo Clinic Stage III-IV and IVST >15mm were independently associated with inferior overall survival (OS) in a multivariable analysis. IVST >15mm was also adversely prognostic for OS in a subgroup of advanced-stage (revised Mayo Clinic stage III-IV) patients in a multivariable analysis (P<0.001). Furthermore, advanced-stage patients with IVST >15mm did not show survival benefit from treatment with bortezomib-based regimens and/or autologous stem-cell transplantation (ASCT). Our study demonstrated that IVST >15mm is adversely prognostic independent of the revised Mayo Clinic staging system in patients with AL amyloidosis. In addition, the degree of IVST might be used as a useful prognostic indicator that can guide the management of patients with AL amyloidosis especially at an advanced stage. Copyright © 2017 Elsevier Ltd. All rights reserved.

The clinical impact of staging bone marrow examination on treatment decisions and prognostic assessment of lymphoma patients.

PubMed

Painter, Dan; Smith, Alexandra; de Tute, Ruth; Crouch, Simon; Roman, Eve; Jack, Andrew

2015-07-01

This study investigates the value of performing a staging bone marrow in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical hodgkin lymphoma (CHL). The results of 3112 staging bone marrow examinations were assessed for impact on prognostic assessment and critical treatment decisions. The detection of marrow involvement altered the disease-specific prognostic index for 4·3% of DLBCL, 6·2% of FL and 0·6% of CHL but marrow involvement in DLBCL was an independent prognostic factor. Knowing the marrow status potentially changed treatment in 92 patients, detection of these patients would have required 854 examinations to be performed. © 2015 John Wiley & Sons Ltd.

Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: multicentre registry study of the Japanese coronary spasm association.

PubMed

Takahashi, Jun; Nihei, Taro; Takagi, Yusuke; Miyata, Satoshi; Odaka, Yuji; Tsunoda, Ryusuke; Seki, Atsushi; Sumiyoshi, Tetsuya; Matsui, Motoyuki; Goto, Toshikazu; Tanabe, Yasuhiko; Sueda, Shozo; Momomura, Shin-ichi; Yasuda, Satoshi; Ogawa, Hisao; Shimokawa, Hiroaki

2015-01-21

Although nitrates are widely used as a concomitant therapy with calcium channel blockers (CCBs) for vasospastic angina (VSA), their prognostic contribution remains unclear. The present study aimed to examine the prognostic impact of chronic nitrate therapy in patients with VSA. A total of 1429 VSA patients (median 66 years; male/female, 1090/339) were enrolled. The primary endpoint was defined as major adverse cardiac events (MACE). The propensity score matching and multivariable Cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. Among the study patients, 695 (49%) were treated with nitrates, including conventional nitrates [e.g. nitroglycerin (GTN), isosorbide mono- and dinitrate] in 551 and nicorandil in 306. Calcium channel blockers were used in >90% of patients. During the median follow-up period of 32 months, 85 patients (5.9%) reached the primary endpoint. Propensity score-matched analysis demonstrated that the cumulative incidence of MACE was comparable between the patients with and those without nitrates [11 vs. 8% at 5 years; hazard ratio (HR): 1.28; 95% confidence interval (CI): 0.72-2.28, P = 0.40]. Although nicorandil itself had a neutral prognostic effect on VSA (HR: 0.80; 95% CI: 0.28-2.27, P = 0.67), multivariable Cox model revealed the potential harm of concomitant use of conventional nitrates and nicorandil (HR: 2.14; 95% CI: 1.02-4.47; P = 0.044), particularly when GTN and nicorandil were simultaneously administered. Chronic nitrate therapy did not improve the long-term prognosis of VSA patients when combined with CCBs. Furthermore, the VSA patients with multiple nitrates would have increased risk for cardiac events. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Childhood adversity impacts on brain subcortical structures relevant to depression.

PubMed

Frodl, Thomas; Janowitz, Deborah; Schmaal, Lianne; Tozzi, Leonardo; Dobrowolny, Henrik; Stein, Dan J; Veltman, Dick J; Wittfeld, Katharina; van Erp, Theo G M; Jahanshad, Neda; Block, Andrea; Hegenscheid, Katrin; Völzke, Henry; Lagopoulos, Jim; Hatton, Sean N; Hickie, Ian B; Frey, Eva Maria; Carballedo, Angela; Brooks, Samantha J; Vuletic, Daniella; Uhlmann, Anne; Veer, Ilya M; Walter, Henrik; Schnell, Knut; Grotegerd, Dominik; Arolt, Volker; Kugel, Harald; Schramm, Elisabeth; Konrad, Carsten; Zurowski, Bartosz; Baune, Bernhard T; van der Wee, Nic J A; van Tol, Marie-Jose; Penninx, Brenda W J H; Thompson, Paul M; Hibar, Derrek P; Dannlowski, Udo; Grabe, Hans J

2017-03-01

Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression. Copyright © 2016. Published by Elsevier Ltd.

Prognostic Impact of the 6th and 7th American Joint Committee on Cancer TNM Staging Systems on Esophageal Cancer Patients Treated With Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nomura, Motoo, E-mail: excell@hkg.odn.ne.jp; Department of Radiation Oncology, Aichi Cancer Center Hospital; Shitara, Kohei

2012-02-01

Purpose: The new 7th edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT. Methods and Materials: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of themore » 6th and 7th staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition. Results: There were significant differences between Stages I and III (p < 0.01) according to both editions. However, the 7th edition poorly distinguishes the prognoses of Stages III and IV (p = 0.36 by multivariate analysis) in comparison to the 6th edition (p = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (p < 0.05). For the Stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for Stage IIA. However, there were no significant differences seen between each prognostic stage. Conclusions: Our study indicates there are several problems with the 7th TNM staging system regarding prognostic factors in patients undergoing CRT.« less

Prognostic value of bone marrow involvement by clonal immunoglobulin gene rearrangements in follicular lymphoma

PubMed Central

Berget, Ellen; Helgeland, Lars; Liseth, Knut; Løkeland, Turid; Molven, Anders; Vintermyr, Olav Karsten

2014-01-01

Aims We aimed to evaluate the prognostic value of routine use of PCR amplification of immunoglobulin gene rearrangements in bone marrow (BM) staging in patients with follicular lymphoma (FL). Methods Clonal rearrangements were assessed by immunoglobulin heavy and light-chain gene rearrangement analysis in BM aspirates from 96 patients diagnosed with FL and related to morphological detection of BM involvement in biopsies. In 71 patients, results were also compared with concurrent flow cytometry analysis. Results BM involvement was detected by PCR in 34.4% (33/96) of patients. The presence of clonal rearrangements by PCR was associated with advanced clinical stage (I–III vs IV; p<0.001), high FL International Prognostic Index (FLIPI) score (0–1, 2 vs ≥3; p=0.003), and detection of BM involvement by morphology and flow cytometry analysis (p<0.001 for both). PCR-positive patients had a significantly poorer survival than PCR-negative patients (p=0.001, log-rank test). Thirteen patients positive by PCR but without morphologically detectable BM involvement, had significantly poorer survival than patients with negative morphology and negative PCR result (p=0.002). The poor survival associated with BM involvement by PCR was independent of the FLIPI score (p=0.007, Cox regression). BM involvement by morphology or flow cytometry did not show a significant impact on survival. Conclusions Our results showed that routine use of PCR-based clonality analysis significantly improved the prognostic impact of BM staging in patients with FL. BM involvement by PCR was also an independent adverse prognostic factor. PMID:25233852

Adverse weather impacts on arable cropping systems

NASA Astrophysics Data System (ADS)

Gobin, Anne

2016-04-01

Damages due to extreme or adverse weather strongly depend on crop type, crop stage, soil conditions and management. The impact is largest during the sensitive periods of the farming calendar, and requires a modelling approach to capture the interactions between the crop, its environment and the occurrence of the meteorological event. The hypothesis is that extreme and adverse weather events can be quantified and subsequently incorporated in current crop models. Since crop development is driven by thermal time and photoperiod, a regional crop model was used to examine the likely frequency, magnitude and impacts of frost, drought, heat stress and waterlogging in relation to the cropping season and crop sensitive stages. Risk profiles and associated return levels were obtained by fitting generalized extreme value distributions to block maxima for air humidity, water balance and temperature variables. The risk profiles were subsequently confronted with yields and yield losses for the major arable crops in Belgium, notably winter wheat, winter barley, winter oilseed rape, sugar beet, potato and maize at the field (farm records) to regional scale (statistics). The average daily vapour pressure deficit (VPD) and reference evapotranspiration (ET0) during the growing season is significantly lower (p < 0.001) and has a higher variability before 1988 than after 1988. Distribution patterns of VPD and ET0 have relevant impacts on crop yields. The response to rising temperatures depends on the crop's capability to condition its microenvironment. Crops short of water close their stomata, lose their evaporative cooling potential and ultimately become susceptible to heat stress. Effects of heat stress therefore have to be combined with moisture availability such as the precipitation deficit or the soil water balance. Risks of combined heat and moisture deficit stress appear during the summer. These risks are subsequently related to crop damage. The methodology of defining

Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma.

PubMed

Chao, Angel; Lai, Chyong-Huey; Wang, Tzu-Hao; Jung, Shih-Ming; Lee, Yun-Shien; Chang, Wei-Yang; Yang, Lan-Yang; Ku, Fei-Chun; Huang, Huei-Jean; Chao, An-Shine; Wang, Chin-Jung; Chang, Ting-Chang; Wu, Ren-Chin

2018-05-03

We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC specimens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified as the strongest prognostic indicator in this patient group. Genomic scar signatures associated with HRD are less frequent in OCCC than in HGSC. Genomic scar signatures associated with HRD have an adverse prognostic impact in patients with OCCC. LOH score is the strongest adverse prognostic factor in patients with OCCC.

On the impact of adverse pressure gradient on the supersonic turbulent boundary layer

NASA Astrophysics Data System (ADS)

Wang, Qian-Cheng; Wang, Zhen-Guo; Zhao, Yu-Xin

2016-11-01

By employing the particle image velocimetry, the mean and turbulent characteristics of a Mach 2.95 turbulent boundary layer are experimentally investigated without the impact of curvature. The physical mechanism with which the streamwise adverse pressure gradient affects the supersonic boundary layer is revealed. The data are compared to that of the concave boundary layer with similar streamwise distributions of wall static pressure to clarify the separate impacts of the adverse pressure gradient and the concave curvature. The logarithmic law is observed to be well preserved for both of the cases. The dip below the logarithmic law is not observed in present investigation. Theoretical analysis indicates that it could be the result of compromise between the opposite impacts of the compression wave and the increased turbulent intensity. Compared to the zero pressure gradient boundary layer, the principal strain rate and the turbulent intensities are increased by the adverse pressure gradient. The shear layer formed due the hairpin packets could be sharpened by the compression wave, which leads to higher principal strain rate and the associated turbulent level. Due to the additional impact of the centrifugal instability brought by the concave wall, even higher turbulent intensities than that of the adverse pressure gradient case are introduced. The existence of velocity modes within the zero pressure gradient boundary layer suggests that the large scale motions are statistically well organized. The generation of new velocity modes due to the adverse pressure gradient indicates that the turbulent structure is changed by the adverse pressure gradient, through which more turbulence production that cannot be effectively predicted by the Reynolds-stress transport equations could be brought.

Ameliorating the biological impacts of childhood adversity: A review of intervention programs.

PubMed

Purewal Boparai, Sukhdip K; Au, Vanessa; Koita, Kadiatou; Oh, Debora Lee; Briner, Susan; Burke Harris, Nadine; Bucci, Monica

2018-05-01

Childhood adversity negatively impacts the biological development of children and has been linked to poor health outcomes across the life course. The purpose of this literature review is to explore and evaluate the effectiveness of interventions that have addressed an array of biological markers and physical health outcomes in children and adolescents affected by adversity. PubMed, CINAHL, PsychInfo, Sociological Abstracts databases and additional sources (Cochrane, WHO, NIH trial registries) were searched for English language studies published between January 2007 and September 2017. Articles with a childhood adversity exposure, biological health outcome, and evaluation of intervention using a randomized controlled trial study design were selected. The resulting 40 intervention studies addressed cortisol outcomes (n = 20) and a range of neurological, epigenetic, immune, and other outcomes (n = 22). Across institutional, foster care, and community settings, intervention programs demonstrated success overall for improving or normalizing morning and diurnal cortisol levels, and ameliorating the impacts of adversity on brain development, epigenetic regulation, and additional outcomes in children. Factors such as earlier timing of intervention, high quality and nurturant parenting traits, and greater intervention engagement played a role in intervention success. This study underlines progress and promise in addressing the health impacts of adversity in children. Ongoing research efforts should collect baseline data, improve retention, replicate studies in additional samples and settings, and evaluate additional variables, resilience factors, mediators, and long-term implications of results. Clinicians should integrate lessons from the intervention sciences for preventing and treating the health effects of adversity in children and adolescents. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed Central

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

PURPOSE We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. METHODS Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. RESULTS The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. CONCLUSION Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury. PMID:26081719

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury.

Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition

PubMed Central

Granell, Miquel; Calvo, Xavier; Garcia-Guiñón, Antoni; Escoda, Lourdes; Abella, Eugènia; Martínez, Clara Mª; Teixidó, Montserrat; Gimenez, Mª Teresa; Senín, Alicia; Sanz, Patricia; Campoy, Desirée; Vicent, Ana; Arenillas, Leonor; Rosiñol, Laura; Sierra, Jorge; Bladé, Joan; de Larrea, Carlos Fernández

2017-01-01

The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the study herein, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analyzed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukemia were reviewed and patients were classified into 4 categories according to the percentage of circulating plasma cells: 0%, 1–4%, 5–20%, and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%), respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, the presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95% CI 2.6–9.3) independently of age, creatinine, the Durie-Salmon system stage and the International Staging System (ISS) stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86×109/L vs. 214×109/L, P<0.0001) and higher bone marrow plasma cells (median 53% vs. 36%, P=0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has a similar adverse prognostic impact as plasma cell leukemia. PMID:28255016

A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

PubMed

Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

2011-06-01

A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse <12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for OS and EFS in this series. We then defined three subgroups with striking different outcomes at 2 years: no adverse factor (favourable, N=36): OS 58%, EFS 45%; one adverse factor (intermediate, N=54): OS 37%, EFS 31%; two or three adverse factors (poor, N=43): OS 12%, EFS 12% (P<10(-4), P=0.001). This new simplified Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

Non-O blood groups can be a prognostic marker of in-hospital and long-term major adverse cardiovascular events in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PubMed

Cetin, Mehmet Serkan; Ozcan Cetin, Elif Hande; Aras, Dursun; Topaloglu, Serkan; Temizhan, Ahmet; Kisacik, Halil Lutfi; Aydogdu, Sinan

2015-09-01

Recent studies have suggested ABO blood type locus as an inherited predictor of thrombosis, cardiovascular risk factors, myocardial infarction. However, data is scarce about the impact of non-O blood groups on prognosis in patients with ST-elevation myocardial infarction (STEMI). Therefore, we aimed to evaluate the prognostic importance of non-O blood groups in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI) METHODS: 1835 consecutive patients who were admitted with acute STEMI between 2010 and 2015 were included and followed-up for a median of 35.6months. The prevalence of hyperlipidemia, total cholesterol, LDL, peak CKMB and no-reflow as well as hospitalization duration were higher in patients with non-O blood groups. Gensini score did not differ between groups. During the in-hospital and long-term follow-up period, MACE, the prevalence of stent thrombosis, non-fatal MI, and mortality were higher in non-O blood groups. In multivariate logistic regression analysis, non-0 blood groups were demonstrated to be independent predictors of in-hospital (OR:2.085 %CI: 1.328-3.274 p=0.001) and long term MACE (OR:2.257 %CI: 1.325-3.759 p<0.001). Kaplan-Meier analysis according to the long-term MACE free survival revealed a higher occurrence of MACE in non-O blood group compared with O blood group (p<0.001, Chi-square: 22.810). Non-O blood groups were determined to be significant prognostic indicators of short- and long-term cardiovascular adverse events and mortality in patients with STEMI undergoing pPCI. In conjunction with other prognostic factors, evaluation of this parameter may improve the risk categorization and tailoring the individual therapy and follow-up in STEMI patient population. Copyright © 2015 Elsevier Ltd. All rights reserved.

Late renal transplant failure: an adverse prognostic factor at initiation of peritoneal dialysis.

PubMed

Sasal, J; Naimark, D; Klassen, J; Shea, J; Bargman, J M

2001-01-01

. Deaths were due mainly to gram-negative peritonitis and cardiovascular disease. We conclude that late failed renal transplant patients starting dialysis are at increased risk of complications and have strikingly higher mortality rates than non-Tx patients. A previously failed kidney transplant can be considered an adverse prognostic factor for patients commencing PD; these patients need to be closely monitored. Although this study was limited to PD patients, the same principles likely apply to fTx patients returning to any form of renal replacement therapy.

The Prognostic Impact of p53 Expression on Sporadic Colorectal Cancer Is Dependent on p21 Status.

PubMed

Kruschewski, Martin; Mueller, Kathrin; Lipka, Sybille; Budczies, Jan; Noske, Aurelia; Buhr, Heinz Johannes; Elezkurtaj, Sefer

2011-03-11

The prognostic value of p53 and p21 expression in colorectal cancer is still under debate. We hypothesize that the prognostic impact of p53 expression is dependent on p21 status. The expression of p53 and p21 was immunohistochemically investigated in a prospective cohort of 116 patients with UICC stage II and III sporadic colorectal cancer. The results were correlated with overall and recurrence-free survival. The mean observation period was 51.8 ± 2.5 months. Expression of p53 was observed in 72 tumors (63%). Overall survival was significantly better in patients with p53-positive carcinomas than in those without p53 expression (p = 0.048). No differences were found in recurrence-free survival (p = 0.161). The p53+/p21- combination was seen in 68% (n = 49), the p53+/p21+ combination in 32% (n = 23). Patients with p53+/p21- carcinomas had significantly better overall and recurrence-free survival than those with p53+/p21+ (p < 0.0001 resp. p = 0.003). Our data suggest that the prognostic impact of p53 expression on sporadic colorectal cancer is dependent on p21 status.

Serum C-reactive protein (CRP) as a simple and independent prognostic factor in extranodal natural killer/T-cell lymphoma, nasal type.

PubMed

Li, Ya-Jun; Li, Zhi-Ming; Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi

2013-01-01

C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI.

Checkpoint kinase 1 expression is an adverse prognostic marker and therapeutic target in MYC-driven medulloblastoma

PubMed Central

Shah, Monil; Mulcahy Levy, Jean M.; Griesinger, Andrea M.; Alimova, Irina; Harris, Peter S.; Birks, Diane K.; Donson, Andrew M.; Davidson, Nathan; Remke, Marc; Taylor, Michael D.; Handler, Michael H.; Foreman, Nicholas K.; Venkataraman, Sujatha; Vibhakar, Rajeev

2016-01-01

Checkpoint kinase 1 (CHK1) is an integral component of the cell cycle as well as the DNA Damage Response (DDR) pathway. Previous work has demonstrated the effectiveness of inhibiting CHK1 with small-molecule inhibitors, but the role of CHK1 mediated DDR in medulloblastoma is unknown. CHK1, both at the mRNA and protein level, is highly expressed in medulloblastoma and elevated CHK1 expression in Group3 medulloblastoma is an adverse prognostic marker. CHK1 inhibition with the small-molecule drug AZD7762, results in decreased cell growth, increased DNA damage and cell apoptosis. Furthermore, AZD7762 acts in synergy with cisplatin in reducing cell proliferation in medulloblastoma. Similar phenotypic changes were observed with another CHK1 inhibitor, PF477736, as well as genetic knockdown using siRNA against CHK1. Treatments with small-molecule inhibitors of CHK1 profoundly modulated the expression of both upstream and downstream target proteins within the CHK1 signaling pathways. This suggests the presence of a feedback loop in activating CHK1. Overall, our results demonstrate that small-molecule inhibition of CHK1 in combination with, cisplatin, is more advantageous than either treatment alone, especially for Group 3 medulloblastoma, and therefore this combined therapeutic approach serves as an avenue for further investigation. PMID:27449089

Checkpoint kinase 1 expression is an adverse prognostic marker and therapeutic target in MYC-driven medulloblastoma.

PubMed

Prince, Eric W; Balakrishnan, Ilango; Shah, Monil; Mulcahy Levy, Jean M; Griesinger, Andrea M; Alimova, Irina; Harris, Peter S; Birks, Diane K; Donson, Andrew M; Davidson, Nathan; Remke, Marc; Taylor, Michael D; Handler, Michael H; Foreman, Nicholas K; Venkataraman, Sujatha; Vibhakar, Rajeev

2016-08-16

Checkpoint kinase 1 (CHK1) is an integral component of the cell cycle as well as the DNA Damage Response (DDR) pathway. Previous work has demonstrated the effectiveness of inhibiting CHK1 with small-molecule inhibitors, but the role of CHK1 mediated DDR in medulloblastoma is unknown. CHK1, both at the mRNA and protein level, is highly expressed in medulloblastoma and elevated CHK1 expression in Group3 medulloblastoma is an adverse prognostic marker. CHK1 inhibition with the small-molecule drug AZD7762, results in decreased cell growth, increased DNA damage and cell apoptosis. Furthermore, AZD7762 acts in synergy with cisplatin in reducing cell proliferation in medulloblastoma. Similar phenotypic changes were observed with another CHK1 inhibitor, PF477736, as well as genetic knockdown using siRNA against CHK1. Treatments with small-molecule inhibitors of CHK1 profoundly modulated the expression of both upstream and downstream target proteins within the CHK1 signaling pathways. This suggests the presence of a feedback loop in activating CHK1. Overall, our results demonstrate that small-molecule inhibition of CHK1 in combination with, cisplatin, is more advantageous than either treatment alone, especially for Group 3 medulloblastoma, and therefore this combined therapeutic approach serves as an avenue for further investigation.

Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition.

PubMed

Granell, Miquel; Calvo, Xavier; Garcia-Guiñón, Antoni; Escoda, Lourdes; Abella, Eugènia; Martínez, Clara Mª; Teixidó, Montserrat; Gimenez, Mª Teresa; Senín, Alicia; Sanz, Patricia; Campoy, Desirée; Vicent, Ana; Arenillas, Leonor; Rosiñol, Laura; Sierra, Jorge; Bladé, Joan; de Larrea, Carlos Fernández

2017-06-01

The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the study herein, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analyzed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukemia were reviewed and patients were classified into 4 categories according to the percentage of circulating plasma cells: 0%, 1-4%, 5-20%, and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%), respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, the presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95% CI 2.6-9.3) independently of age, creatinine, the Durie-Salmon system stage and the International Staging System (ISS) stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86×10 9 /L vs 214×10 9 /L, P <0.0001) and higher bone marrow plasma cells (median 53% vs 36%, P =0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has a similar adverse prognostic impact as plasma cell leukemia. Copyright© Ferrata Storti Foundation.

Psychosocial impact of prognostic genetic testing in the care of uveal melanoma patients: protocol of a controlled prospective clinical observational study.

PubMed

Erim, Yesim; Scheel, Jennifer; Breidenstein, Anja; Metz, Claudia Hd; Lohmann, Dietmar; Friederich, Hans-Christoph; Tagay, Sefik

2016-07-07

Uveal melanoma patients with a poor prognosis can be detected through genetic analysis of the tumor, which has a very high sensitivity. A large number of patients with uveal melanoma decide to receive information about their individual risk and therefore routine prognostic genetic testing is being carried out on a growing number of patients. It is obvious that a positive prediction for recidivism in the future will emotionally burden the respective patients, but research on the psychosocial impact of this innovative method is lacking. The aim of the current study is therefore to investigate the psychosocial impact (psychological distress and quality of life) of prognostic genetic testing in patients with uveal melanoma. This study is a non-randomized controlled prospective clinical observational trial. Subjects are patients with uveal melanoma, in whom genetic testing is possible. Patients who consent to genetic testing are allocated to the intervention group and patients who refuse genetic testing form the observational group. Both groups receive cancer therapy and psycho-oncological intervention when needed. The psychosocial impact of prognostic testing is investigated with the following variables: resilience, social support, fear of tumor progression, depression, general distress, cancer-specific and general health-related quality of life, attitude towards genetic testing, estimation of the perceived risk of metastasis, utilization and satisfaction with psycho-oncological crisis intervention, and sociodemographic data. Data are assessed preoperatively (at initial admission in the clinic) and postoperatively (at discharge from hospital after surgery, 6-12 weeks, 6 and 12 months after initial admission). Genetic test results are communicated 6-12 weeks after initial admission to the clinic. We created optimal conditions for investigation of the psychosocial impact of prognostic genetic testing. This study will provide information on the course of disease and

Intrahepatic cholangiocarcinoma prognostic determination using pre-operative serum C-reactive protein levels.

PubMed

Lin, Zi-Ying; Liang, Zhen-Xing; Zhuang, Pei-Lin; Chen, Jie-Wei; Cao, Yun; Yan, Li-Xu; Yun, Jing-Ping; Xie, Dan; Cai, Mu-Yan

2016-10-12

Serum C-reactive protein (CRP), an acute inflammatory response biomarker, has been recognized as an indicator of malignant disease progression. However, the prognostic significance of CRP levels collected before tumor removal in intrahepatic cholangiocarcinoma requires further investigation. We sampled the CRP levels in 140 patients with intrahepatic cholangiocarcinoma who underwent hepatectomies with regional lymphadenectomies between 2006 and 2013. A retrospective analysis of the clinicopathological data was performed. We focused on the impact of serum CRP on the patients' cancer-specific survival and recurrence-free survival rates. High levels of preoperative serum CRP were significantly associated with well-established clinicopathologic features, including gender, advanced tumor stage, and elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P < 0.05). Univariate analysis demonstrated a significant association between high levels of serum CRP and adverse cancer-specific survival (P = 0.001) and recurrence-free survival (P < 0.001). In patients with stage I/II intrahepatic cholangiocarcinoma, the serum CRP level was a prognostic indicator for cancer-specific survival. In patients with stage I/II or stage III/IV, the serum CRP level was a prognostic indicator for recurrence-free survival (P < 0.05). Additionally, multivariate analysis identified serum CRP level in intrahepatic cholangiocarcinoma as an independent prognostic factor (P < 0.05). We confirmed a significant association of elevated pre-operative CRP levels with poor clinical outcomes for the tested patients with intrahepatic cholangiocarcinoma. Our results indicate that the serum CRP level may represent a useful factor for patient stratification in intrahepatic cholangiocarcinoma management.

The psychological impact of chronic environmental adversity: Responding to prolonged drought.

PubMed

Stain, Helen J; Kelly, Brian; Carr, Vaughan J; Lewin, Terry J; Fitzgerald, Michael; Fragar, Lyn

2011-12-01

The health effects of chronic environmental adversity have received insufficient attention, particularly those associated with the psychological impact of drought. Resilience or adaptive response to drought has received even less attention than vulnerability factors. This research examined factors associated with drought impact in rural and remote Australian communities. In 2008 postal surveys were completed by 302 adults (mean age 53 years; 57% female, 77% married) living in rural areas of prolonged drought exposure. Outcome measures were: (i) psychological distress (Kessler 10) and (ii) an index of concern or worry about drought. A range of predictor variables were assessed: adaptability (hopefulness, neuroticism), other adverse events, personal support and community connectedness, and sense of place, as a measure of connection to the local environment. Predictors of drought related worry differed from those associated with psychological distress levels. The former included socio-economic factors (living on a farm [Odds Ratio, OR 3.09], current employment [OR 3.64]), personal psychological characteristics (neuroticism [OR 1.29]), and greater connection with the environment (sense of place [OR 1.05]). On the other hand, psychological distress was associated chiefly with personal factors, such as higher neuroticism [OR 1.92], lower levels of hopefulness [OR 0.28], and lower perceived social support and community connectedness [OR 0.39]. Practical financial, employment and family factors were identified as important elements of drought impact, as to a lesser extent was sense of place, reflecting a confrontation with the consequences of chronic environmental degradation, while personal hopefulness may help mitigate the psychological impact of such adversity. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Prognostic Impact of Visceral Fat Amount and Branched-Chain Amino Acids (BCAA) in Hepatocellular Carcinoma.

PubMed

Higashi, Takaaki; Hayashi, Hiromitsu; Kaida, Takayoshi; Arima, Kota; Takeyama, Hideaki; Taki, Katsunobu; Izumi, Daisuke; Tokunaga, Ryuma; Kosumi, Keisuke; Nakagawa, Shigeki; Okabe, Hirohisa; Imai, Katsunobu; Nitta, Hidetoshi; Hashimoto, Daisuke; Chikamoto, Akira; Beppu, Toru; Baba, Hideo

2015-12-01

Dysregulation of lipid and amino acid metabolism in patients with liver diseases results in obesity-related carcinogenesis and decreased levels of branched-chain amino acids (BCAA), respectively. This study assessed the clinical and prognostic impact of visceral fat amount (VFA) and its association with amino acid metabolism in patients with hepatocellular carcinoma (HCC). In this study, 215 patients who underwent hepatic resection for HCC were divided into two groups based on VFA criteria for metabolic abnormalities in Japan. Computed tomography was used to measure VFA at the third lumbar vertebra in the inferior direction. Of the 215 patients, 132 had high and 83 had low VFA. High VFA was significantly associated with older age and higher body mass index (BMI), subcutaneous fat amount, and BCAA, but not with liver function, nutrient status, or tumoral factors. VFA was positively correlated with BMI (P < 0.0001; r = 0.63) and BCAA levels (P < 0.0001; r = 0.29). Overall survival was significantly greater in the high than in the low VFA group (P = 0.002). Multivariate analyses showed that high VFA [hazard ratio (HR) 7.06; P = 0.024] and neutrophil/lymphocyte ratio (HR 3.47; P = 0.049) were significantly prognostic of overall survival, whereas subcutaneous fat amount, BMI, BCAA, serum albumin, and prognostic nutritional index were not. High VFA was associated with a high BCAA level, with high VFA prognostic of improved overall survival in Japanese patients with HCC.

Serum C-Reactive Protein (CRP) as a Simple and Independent Prognostic Factor in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

PubMed Central

Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi

2013-01-01

Background C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). Methods We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Results Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Conclusions Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI. PMID:23724031

A new prognostic model for chemotherapy-induced febrile neutropenia.

PubMed

Ahn, Shin; Lee, Yoon-Seon; Lee, Jae-Lyun; Lim, Kyung Soo; Yoon, Sung-Cheol

2016-02-01

The objective of this study was to develop and validate a new prognostic model for febrile neutropenia (FN). This study comprised 1001 episodes of FN: 718 for the derivation set and 283 for the validation set. Multivariate logistic regression analysis was performed with unfavorable outcome as the primary endpoint and bacteremia as the secondary endpoint. In the derivation set, risk factors for adverse outcomes comprised age ≥ 60 years (2 points), procalcitonin ≥ 0.5 ng/mL (5 points), ECOG performance score ≥ 2 (2 points), oral mucositis grade ≥ 3 (3 points), systolic blood pressure <90 mmHg (3 points), and respiratory rate ≥ 24 breaths/min (3 points). The model stratified patients into three severity classes, with adverse event rates of 6.0 % in class I (score ≤ 2), 27.3 % in class II (score 3-8), and 67.9 % in class III (score ≥ 9). Bacteremia was present in 1.1, 11.5, and 29.8 % of patients in class I, II, and III, respectively. The outcomes of the validation set were similar in each risk class. When the derivation and validation sets were integrated, unfavorable outcomes occurred in 5.9 % of the low-risk group classified by the new prognostic model and in 12.2 % classified by the Multinational Association for Supportive Care in Cancer (MASCC) risk index. With the new prognostic model, we can classify patients with FN into three classes of increasing adverse outcomes and bacteremia. Early discharge would be possible for class I patients, short-term observation could safely manage class II patients, and inpatient admission is warranted for class III patients.

The moderating impact of childhood adversity profiles and conflict on psychological health and suicidal behaviour in the Northern Ireland population.

PubMed

McLafferty, Margaret; O'Neill, Siobhan; Murphy, Sam; Armour, Cherie; Ferry, Finola; Bunting, Brendan

2018-04-01

Childhood adversities are key etiological factors in the onset and persistence of psychopathology. In Northern Ireland the Troubles also impacted on the population's psychological health. This study used data from the Northern Ireland Study of Health and Stress a collaborative epidemiological study which used the WMH-CIDI to assess mental health disorders in a nationally representative sample (Part 2, n = 1986). The aims of the study were to assess co-occurrences of childhood adversities and investigate the impact of adversity profiles and conflict experience on psychopathology and suicidal behaviour. Latent Class Analysis uncovered 3 discrete childhood adversity profiles, a low, medium, and high risk class. Individuals from higher risk adversity profiles displayed significantly increased odds of having psychological problems, with conflict exposure also impacting on psychopathology. However, the study revealed that the impact of conflict exposure on suicidal behaviour was moderated by latent class membership and that some adversity may actually be protective. The findings highlight the need to consider that, while adversity can have a negative impact on psychopathology, a lack of adversity early in life may hinder some people from developing adequate coping strategies. Further research is required to identify adversity patterns and other interacting factors that are protective. Copyright © 2018 Elsevier B.V. All rights reserved.

Impact of childhood adversities on the short-term course of illness in psychotic spectrum disorders.

PubMed

Schalinski, Inga; Fischer, Yolanda; Rockstroh, Brigitte

2015-08-30

Accumulating evidence indicates an impact of childhood adversities on the severity and course of mental disorders, whereas this impact on psychotic disorders remains to be specified. Effects of childhood adversities on comorbidity, on symptom severity of the Positive and Negative Syndrome Scale and global functioning across four months (upon admission, 1 and 4 months after initial assessment), as well as the course of illness (measured by the remission rate, number of re-hospitalizations and dropout rate) were evaluated in 62 inpatients with psychotic spectrum disorders. Adverse experiences (of at least 1 type) were reported by 73% of patients. Patients with higher overall level of childhood adversities (n=33) exhibited more co-morbid disorders, especially alcohol/substance abuse and dependency, and higher dropout rates than patients with a lower levels of adverse experiences (n=29), together with higher levels of positive symptoms and symptoms of excitement and disorganization. Emotional and physical neglect were particularly related to symptom severity. Results suggest that psychological stress in childhood affects the symptom severity and, additionally, a more unfavorable course of disorder in patients diagnosed with psychoses. This impact calls for its consideration in diagnostic assessment and psychiatric care. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Biomarkers of adverse drug reactions.

PubMed

Carr, Daniel F; Pirmohamed, Munir

2018-02-01

Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

The prognostic impact of sex on surgically resected non-small cell lung cancer depends on clinicopathologic characteristics.

PubMed

Sterlacci, William; Tzankov, Alexandar; Veits, Lothar; Oberaigner, Wilhelm; Schmid, Thomas; Hilbe, Wolfgang; Fiegl, Michael

2011-04-01

The increasing incidence of lung cancer in women and their supposed survival advantage over men requires clarification of the significance of sex. Age, stage, histologic features, differentiation grade, and Ki-67 index were assessed in 405 surgically resected non-small cell lung cancers (NSCLCs) using a standardized tissue microarray platform. Women were associated with well/moderate tumor differentiation, a Ki-67 index of 3% or less, and adenocarcinoma histologic features. Female sex predicted increased survival time only by univariate analysis. Stratified by sex, increased survival was noted for women older than 64 years, with a tumor at postsurgical International Union Against Cancer stage I, with adenocarcinoma histologic features, with well- or moderately differentiated tumors, or with a Ki-67 index of 3% or less. Sex is not an independent prognostic parameter for patients with surgically resected NSCLC. Sex-linked differences are associated with other factors, thus simulating a prognostic impact of sex. This study elucidates sex-specific interactions between patient and tumor characteristics, which are pivotal toward improving prognostic accuracy, individualized therapies, and screening efforts.

Prediction of Outcome after Moderate and Severe Traumatic Brain Injury: External Validation of the IMPACT and CRASH Prognostic Models

PubMed Central

Roozenbeek, Bob; Lingsma, Hester F.; Lecky, Fiona E.; Lu, Juan; Weir, James; Butcher, Isabella; McHugh, Gillian S.; Murray, Gordon D.; Perel, Pablo; Maas, Andrew I.R.; Steyerberg, Ewout W.

2012-01-01

Objective The International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict outcome after traumatic brain injury (TBI) but have not been compared in large datasets. The objective of this is study is to validate externally and compare the IMPACT and CRASH prognostic models for prediction of outcome after moderate or severe TBI. Design External validation study. Patients We considered 5 new datasets with a total of 9036 patients, comprising three randomized trials and two observational series, containing prospectively collected individual TBI patient data. Measurements Outcomes were mortality and unfavourable outcome, based on the Glasgow Outcome Score (GOS) at six months after injury. To assess performance, we studied the discrimination of the models (by AUCs), and calibration (by comparison of the mean observed to predicted outcomes and calibration slopes). Main Results The highest discrimination was found in the TARN trauma registry (AUCs between 0.83 and 0.87), and the lowest discrimination in the Pharmos trial (AUCs between 0.65 and 0.71). Although differences in predictor effects between development and validation populations were found (calibration slopes varying between 0.58 and 1.53), the differences in discrimination were largely explained by differences in case-mix in the validation studies. Calibration was good, the fraction of observed outcomes generally agreed well with the mean predicted outcome. No meaningful differences were noted in performance between the IMPACT and CRASH models. More complex models discriminated slightly better than simpler variants. Conclusions Since both the IMPACT and the CRASH prognostic models show good generalizability to more recent data, they are valid instruments to quantify prognosis in TBI. PMID:22511138

Recurrent ischemia across the spectrum of acute coronary syndromes: prevalence and prognostic significance of (re-)infarction and ST-segment changes in a large contemporary registry.

PubMed

Yan, Andrew T; Steg, Philippe Gabriel; Fitzgerald, Gordon; Feldman, Laurent J; Eagle, Kim A; Gore, Joel M; Anderson, Frederick A; López-Sendón, Jose; Gurfinkel, Enrique P; Brieger, David; Goodman, Shaun G

2010-11-05

There are limited recent data on the prevalence and potentially different adverse impact of the various types of recurrent ischemia (RI) in unselected patients with acute coronary syndromes(ACS). We examined the clinical features and treatment associated with, and the differential prognostic impact of, the various types of RI in unselected patients across the broad spectrum of ACS in the contemporary era. The Global Registry of Acute Coronary Events (GRACE) was a prospective, multinational registry of patients hospitalized for ACS. Data were collected on standardized case report forms. Of the 29,400 ACS patients enrolled in May 2000-March 2007, 21% developed RI; 2.4%, 4.9%, and 16% had myocardial (re-)infarction [(re-)MI], RI with ST-segment changes, and RI without ST-segment changes (not mutually exclusive), respectively. Rates of in-hospital mortality and complications, and 6-month mortality were significantly higher among patients with RI compared to those without; the rates were highest for patients who developed (re-)MI, followed by those with RI and ST-segment changes. After adjusting for other validated prognosticators in the GRACE risk score, all three types of RI retained an independent association with both higher in-hospital and post-discharge 6-month mortality. Early revascularization was associated with lower in-hospital mortality only in the group with (re-)MI (P for interaction=0.003). Despite the current use of intensive medical therapies, RI remains a common and serious consequence across the spectrum of ACS. Different types of RI confer a variable adverse prognostic impact. Re-MI is associated with the worst outcome, which appears to be mitigated by early revascularization. Our findings underscore the persistent need to improve the treatment of ACS. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

The impact of childhood adversities on anxiety and depressive disorders in adulthood.

PubMed

Marackova, Marketa; Prasko, Jan; Matousek, Stanislav; Latalova, Klara; Hruby, Radovan; Holubova, Michaela; Slepecky, Milos; Vrbova, Kristyna; Grambal, Ales

2016-12-01

The childhood adversities model is generally accepted as a predictor of adult psychopathology vulnerability. It stems from child development theories, but the question remains as of how well solid research supports it. The aim of this article is to give a review of the studies concerning childhood adversities and their impact on the development of anxiety disorders and major depressive disorder in adulthood. A computerized search of the MEDLINE database of publications up to 31 March 2016 was done, using the keywords "childhood adversities, abuse, maltreatment, bullying" and "anxiety disorders, depressive disorder". No backward time constraints were used. Non-original studies, conference abstracts, books and book chapters, commentaries, and dissertations were excluded. The influence of childhood adversities on later age psychopathology is examined in five categories: the negative family atmosphere, abuse, loss of a close person, the social difficulties, and problems at school (including, most importantly bullying). The majority of studies confirmed the connection between childhood adversities and anxiety and depression disorders in adulthood. The character of the adversities is not, apparently, a specific predictor for a concrete psychopathology. Multiple adversities are more frequently connected with depressive and anxiety disorders in adulthood, cumulating together in broader adverse context. Childhood adversities were found to increase vulnerability to the distress, depression, fear and anxiety later in the life. However, specific correlations between a given childhood adversity and a specific form of depression or anxiety disorder were either not found or weak. This is in line with the generally accepted view considering each of these factors a non-specific stressor increasing vulnerability to mood and affect disorders later in life.

Tumour functional sphericity from PET images: prognostic value in NSCLC and impact of delineation method.

PubMed

Hatt, Mathieu; Laurent, Baptiste; Fayad, Hadi; Jaouen, Vincent; Visvikis, Dimitris; Le Rest, Catherine Cheze

2018-04-01

Sphericity has been proposed as a parameter for characterizing PET tumour volumes, with complementary prognostic value with respect to SUV and volume in both head and neck cancer and lung cancer. The objective of the present study was to investigate its dependency on tumour delineation and the resulting impact on its prognostic value. Five segmentation methods were considered: two thresholds (40% and 50% of SUV max ), ant colony optimization, fuzzy locally adaptive Bayesian (FLAB), and gradient-aided region-based active contour. The accuracy of each method in extracting sphericity was evaluated using a dataset of 176 simulated, phantom and clinical PET images of tumours with associated ground truth. The prognostic value of sphericity and its complementary value with respect to volume for each segmentation method was evaluated in a cohort of 87 patients with stage II/III lung cancer. Volume and associated sphericity values were dependent on the segmentation method. The correlation between segmentation accuracy and sphericity error was moderate (|ρ| from 0.24 to 0.57). The accuracy in measuring sphericity was not dependent on volume (|ρ| < 0.4). In the patients with lung cancer, sphericity had prognostic value, although lower than that of volume, except for that derived using FLAB for which when combined with volume showed a small improvement over volume alone (hazard ratio 2.67, compared with 2.5). Substantial differences in patient prognosis stratification were observed depending on the segmentation method used. Tumour functional sphericity was found to be dependent on the segmentation method, although the accuracy in retrieving the true sphericity was not dependent on tumour volume. In addition, even accurate segmentation can lead to an inaccurate sphericity value, and vice versa. Sphericity had similar or lower prognostic value than volume alone in the patients with lung cancer, except when determined using the FLAB method for which there was a small

Cognitive predictors and age-based adverse impact among business executives.

PubMed

Klein, Rachael M; Dilchert, Stephan; Ones, Deniz S; Dages, Kelly D

2015-09-01

Age differences on measures of general mental ability and specific cognitive abilities were examined in 2 samples of job applicants to executive positions as well as a mix of executive/nonexecutive positions to determine which predictors might lead to age-based adverse impact in making selection and advancement decisions. Generalizability of the pattern of findings was also investigated in 2 samples from the general adult population. Age was negatively related to general mental ability, with older executives scoring lower than younger executives. For specific ability components, the direction and magnitude of age differences depended on the specific ability in question. Older executives scored higher on verbal ability, a measure most often associated with crystallized intelligence. This finding generalized across samples examined in this study. Also, consistent with findings that fluid abilities decline with age, older executives scored somewhat lower on figural reasoning than younger executives, and much lower on a letter series test of inductive reasoning. Other measures of inductive reasoning, such as Raven's Advanced Progressive Matrices, also showed similar age group mean differences across settings. Implications for employee selection and adverse impact on older job candidates are discussed. (c) 2015 APA, all rights reserved).

Prognostic significance of extranodal extension in head and neck squamous cell carcinoma cN0 patients with occult metastatic neck nodes.

PubMed

Lop, Joan; Rigó, Antoni; Codina, Alberto; de Juan, Julia; Quer, Miquel; León, Xavier

Extranodal extension in nodal metastases is an independent adverse prognostic factor in head and neck squamous cell carcinoma patients. However, few studies specifically address the subgroup of patients with no clinical evidence of nodal disease. We retrospectively analysed data from 348 head and neck squamous cell carcinoma patients without any previous treatment and lacking clinical or radiological evidence of neck node metastases during the initial workup, treated with an elective neck dissection between 1992-2014. The incidence of occult metastatic neck nodes with extranodal extension and the impact of extranodal extension in survival were evaluated. The proportion of patients with occult neck node metastases was 33%. Of these, 23.5% had at least one metastatic neck node with extranodal extension. There were significant differences in the disease-specific survival rate according to neck node status. Five-year disease-specific survival for patients without histopathological metastases was 90%, for patients with occult neck node metastases without extranodal extension it was 71.2%, and for patients with occult neck node metastases with extranodal extension it was 25.9% (P=.0001). The multivariate analysis revealed that the presence of occult node metastases with extranodal extension was the factor with strongest impact on survival. The inclusion of the extranodal extension as a criterion of histopathological evaluation in the 8th TNM classification edition improves the prognostic capacity compared to previous TNM editions. Appearance of metastatic neck nodes with extranodal extension is an adverse prognostic factor in head and neck squamous cell carcinoma patients without clinical evidence of regional disease during the initial workup of the tumour. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

PD-L1 expression and prognostic impact in glioblastoma

PubMed Central

Nduom, Edjah K.; Wei, Jun; Yaghi, Nasser K.; Huang, Neal; Kong, Ling-Yuan; Gabrusiewicz, Konrad; Ling, Xiaoyang; Zhou, Shouhao; Ivan, Cristina; Chen, Jie Qing; Burks, Jared K.; Fuller, Greg N.; Calin, George A.; Conrad, Charles A.; Creasy, Caitlin; Ritthipichai, Krit; Radvanyi, Laszlo; Heimberger, Amy B.

2016-01-01

Background Therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule-4 (CTLA-4) and PD-1/PD-L1 has demonstrated tumor regression in clinical trials, and phase 2 trials are ongoing in glioblastoma (GBM). Previous reports have suggested that responses are more frequent in patients with tumors that express PD-L1; however, this has been disputed. At issue is the validation of PD-L1 biomarker assays and prognostic impact. Methods Using immunohistochemical analysis, we measured the incidence of PD-L1 expression in 94 patients with GBM. We categorized our results according to the total number of PD-L1-expressing cells within the GBMs and then validated this finding in ex vivo GBM flow cytometry with further analysis of the T cell populations. We then evaluated the association between PD-L1 expression and median survival time using the protein expression datasets and mRNA from The Cancer Genome Atlas. Results The median percentage of PD-L1-expressing cells in GBM by cell surface staining is 2.77% (range: 0%–86.6%; n = 92), which is similar to the percentage found by ex vivo flow cytometry. The majority of GBM patients (61%) had tumors with at least 1% or more PD-L1-positive cells, and 38% had at least 5% or greater PD-L1 expression. PD-L1 is commonly expressed on the GBM-infiltrating T cells. Expression of both PD-L1 and PD-1 are negative prognosticators for GBM outcome. Conclusions The incidence of PD-L1 expression in GBM patients is frequent but is confined to a minority subpopulation, similar to other malignancies that have been profiled for PD-L1 expression. Higher expression of PD-L1 is correlated with worse outcome. PMID:26323609

Prognosis Research Strategy (PROGRESS) 3: prognostic model research.

PubMed

Steyerberg, Ewout W; Moons, Karel G M; van der Windt, Danielle A; Hayden, Jill A; Perel, Pablo; Schroter, Sara; Riley, Richard D; Hemingway, Harry; Altman, Douglas G

2013-01-01

Prognostic models are abundant in the medical literature yet their use in practice seems limited. In this article, the third in the PROGRESS series, the authors review how such models are developed and validated, and then address how prognostic models are assessed for their impact on practice and patient outcomes, illustrating these ideas with examples.

The degree of circumferential tumour involvement as a prognostic factor in oesophageal cancer.

PubMed

Sillah, Karim; Pritchard, Susan A; Watkins, Gillian R; McShane, James; West, Catharine M; Page, Richard; Welch, Ian M

2009-08-01

Tumour length is an adverse prognostic factor in oesophageal cancer. However, the prognostic role of the degree of oesophageal circumference (DOC) involved by tumour with or without resection margin invasion is not clear. This work assessed the relationship between DOC involved by tumour, clinico-pathological variables and prognosis. The clinico-pathological details of 320 patients who underwent potentially curative oesophagogastrectomy for cancer between 1994 and 2007 were analysed. The DOC involved with tumour measured macroscopically on the resected specimen was classified as small (<2.5 cm, n = 115), large (> or = 2.5 cm, n = 144) or circumferential (i.e. involving the whole circumference, n = 61). Univariate and multivariate survival analyses were carried out. The DOC with tumour was higher in ulcerating tumours than stenosing or polypoidal types (p = 0.017). Tumour length, T-stage, neoadjuvant chemotherapy and vascular invasion were independently associated with DOC with tumour on multivariate analysis (p < 0.05 for all). DOC > or = 2.5 cm was an adverse prognostic factor in univariate analysis (p = 0.002) with a hazard ratio of 1.52 [95% CI 1.13-2.04] compared with those <2.5 cm. Circumferential tumours had a similar prognosis to tumours > or = 2.5 cm (p = 0.60). The prognostic significance of DOC with tumour was lost in multivariate analysis where the factors retaining independence were patient age, T-stage, lymph node metastasis, vascular invasion and positive resection margins. However, when patients were stratified by use of neoadjuvant chemotherapy (n = 121), the DOC with tumour retained prognostic significance on multivariate analysis in the 199 patients who did not undergo neoadjuvant chemotherapy (p = 0.04). The DOC with tumour appears to provide prognostic information in oesophageal cancer surgery, especially in patients who do not undergo preoperative chemotherapy.

Newly identified poor prognostic factors for adult T-cell leukemia-lymphoma treated with allogeneic hematopoietic stem cell transplantation.

PubMed

Tokunaga, Masahito; Uto, Hirofumi; Takeuchi, Shogo; Nakano, Nobuaki; Kubota, Ayumu; Tokunaga, Mayumi; Takatsuka, Yoshifusa; Seto, Masao; Ido, Akio; Utsunomiya, Atae

2017-01-01

To explore pre-transplantation prognostic factors for adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 70 patients at our institute (63 acute type and seven lymphoma type patients). Forty-five patients died after HSCT and the three-year overall survival (OS) rate was 35.2%. By univariate analysis, the adverse prognostic factors for OS were performance status ≥2, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score ≥3, European Group for Blood and Marrow Transplantation (EBMT) risk score ≥5, HSCT from an HLA-mismatched donor, serum soluble interleukin-2 receptor (sIL-2R) level ≥10,000 U/mL, lymphocyte count ≥4000/μL, and hemoglobin <9 g/dL at the time of HSCT. EBMT risk score and sIL-2R were identified as significant adverse prognostic factors using multivariate analysis. This analysis clearly demonstrates for the first time that HCT-CI and EBMT risk scores are reliable prognostic factors for ATL patients receiving allo-HSCT.

Prognostic factors of whiplash-associated disorders: a systematic review of prospective cohort studies.

PubMed

Scholten-Peeters, Gwendolijne G M; Verhagen, Arianne P; Bekkering, Geertruida E; van der Windt, Daniëlle A W M; Barnsley, Les; Oostendorp, Rob A B; Hendriks, Erik J M

2003-07-01

We present a systematic review of prospective cohort studies. Our aim was to assess prognostic factors associated with functional recovery of patients with whiplash injuries. The failure of some patients to recover following whiplash injury has been linked to a number of prognostic factors. However, there is some inconsistency in the literature and there have been no systematic attempts to analyze the level of evidence for prognostic factors in whiplash recovery. Studies were selected for inclusion following a comprehensive search of MEDLINE, EMBASE, CINAHL, the database of the Dutch Institute of Allied Health Professions up until April 2002 and hand searches of the reference lists of retrieved articles. Studies were selected if the objective was to assess prognostic factors associated with recovery; the design was a prospective cohort study; the study population included at least an identifiable subgroup of patients suffering from a whiplash injury; and the paper was a full report published in English, German, French or Dutch. The methodological quality was independently assessed by two reviewers. A study was considered to be of 'high quality' if it satisfied at least 50% of the maximum available quality score. Two independent reviewers extracted data and the association between prognostic factors and functional recovery was calculated in terms of risk estimates. Fifty papers reporting on twenty-nine cohorts were included in the review. Twelve cohorts were considered to be of 'high quality'. Because of the heterogeneity of patient selection, type of prognostic factors and outcome measures, no statistical pooling was able to be performed. Strong evidence was found for high initial pain intensity being an adverse prognostic factor. There was strong evidence that for older age, female gender, high acute psychological response, angular deformity of the neck, rear-end collision, and compensation not being associated with an adverse prognosis. Several physical (e

Impact of a labor and delivery safety bundle on a modified adverse outcomes index.

PubMed

Tolcher, Mary Catherine; Torbenson, Vanessa E; Weaver, Amy L; McGree, Michaela E; El-Nashar, Sherif A; Nesbitt, Katharine M; Gostout, Bobbie S; Famuyide, Abimbola O

2016-03-01

The Obstetrics Adverse Outcomes Index was designed to measure the quality of perinatal care and includes 10 adverse events that may occur at or around the time of delivery. We hypothesized that adverse outcomes in the labor and delivery suite, including hypoxic ischemic encephalopathy, could be decreased with a combination of interventions, even among high-risk pregnancies. The objective of the study was to evaluate the impact of a labor and delivery care bundle on adverse obstetrics outcomes as measured by a modified Obstetrics Adverse Outcomes Index, Weighted Adverse Outcomes Index, and Severity Index. This is a retrospective cohort study including all women who delivered at our academic, tertiary care institution over a 3 year period of time, before and after the implementation of an intervention to decrease adverse outcomes. Outcome measures consisted of previously reported indices that were modified including the addition of hypoxic ischemic encephalopathy. The adverse outcomes index is a percentage of deliveries with 1 or more adverse events, the weighted adverse outcomes index is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries, and the severity index is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. A segmented regression analysis was utilized to evaluate the differences in the level and trend of each index before and after our intervention using calendar month as the unit of analysis. During the study period, 5826 deliveries met inclusion criteria. Comparing the pre- and postintervention periods, high-risk pregnancy was more common in the postintervention period (73.5% vs 79.4%, P < .001). Overall, there was a decrease in both the Modified Weighted Adverse Outcomes Index (P = .0497) and the Modified Severity Index (P = 0.01) comparing the pre- and postintervention periods; there was no difference in the Modified Adverse Outcomes Index (P = .43

Impact of early life adversity on EMG stress reactivity of the trapezius muscle.

PubMed

Luijcks, Rosan; Vossen, Catherine J; Roggeveen, Suzanne; van Os, Jim; Hermens, Hermie J; Lousberg, Richel

2016-09-01

Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0-11 years) and adolescence (12-17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability.Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies.

Impact of health care adversity on providers: Lessons learned from a staff support program.

PubMed

Trent, Maxine; Waldo, Kimberly; Wehbe-Janek, Hania; Williams, Daniel; Hegefeld, Wendy; Havens, Lisa

2016-08-01

Health care providers often experience traumatic events and adversity that can have negative emotional impacts on the profession and on patients. These impacts are typically multifaceted and can result from many different events, such as unanticipated outcomes, licensing board complaints, claims, and litigation. Because health care providers are exposed to diverse situations, they require adequate and timely support, imperative for provider resilience and patient safety. This study evaluated the success of an institution's second victim health care support program and best practices in responding to these traumatic experiences effectively. Twenty faculty and medical residents who utilized the support program at a large hospital system located in Central Texas from 2001 to 2012 participated in 1 of 6 focus groups. Qualitative data were collected from these groups to describe program requirements for the adequate delivery of health care adversity support and necessary program improvements. Responses were first transcribed verbatim. Each research team member analyzed data using a thematic framework approach. This approach helped to characterize traumatic experiences and to design a support system. The results revealed that (1) provider experiences are traumatic, (2) it is necessary to communicate an adverse event in a confidential and timely manner, preferably with a peer, (3) preemptive education regarding risk management and the legal process is helpful, and (4) there is a need for further support of the specific experience of a board complaint. Focus group data indicated the complexity of the emotional impact of traumatic experiences. Specific program components are needed to create best practices for providers affected by health care adversity, including support when providers face board complaints. The program's unique combination of support and education allowed us to expand upon leading national health care adversity programs. © 2016 American Society for

Vehicle Integrated Prognostic Reasoner (VIPR) Final Report

NASA Technical Reports Server (NTRS)

Bharadwaj, Raj; Mylaraswamy, Dinkar; Cornhill, Dennis; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

2013-01-01

A systems view is necessary to detect, diagnose, predict, and mitigate adverse events during the flight of an aircraft. While most aircraft subsystems look for simple threshold exceedances and report them to a central maintenance computer, the vehicle integrated prognostic reasoner (VIPR) proactively generates evidence and takes an active role in aircraft-level health assessment. Establishing the technical feasibility and a design trade-space for this next-generation vehicle-level reasoning system (VLRS) is the focus of our work.

Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals

PubMed Central

Han, Donghee; Hartaigh, Bríain Ó; Gransar, Heidi; Lee, Ji Hyun; Rizvi, Asim; Baskaran, Lohendran; Schulman-Marcus, Joshua; Dunning, Allison; Achenbach, Stephan; Al-Mallah, Mouaz H; Berman, Daniel S; Budoff, Matthew J; Cademartiri, Filippo; Maffei, Erica; Callister, Tracy Q; Chinnaiyan, Kavitha; Chow, Benjamin J W; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Kaufmann, Philipp A; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Kim, Yong-Jin; Leipsic, Jonathon; Feuchtner, Gudrun; Cury, Ricardo C; Pontone, Gianluca; Andreini, Daniele; Marques, Hugo; Rubinshtein, Ronen; Hindoyan, Niree; Jones, Erica C; Gomez, Millie; Lin, Fay Y; Chang, Hyuk-Jae; Min, James K

2018-01-01

Abstract Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1–49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18–41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults. PMID:28977374

Comparison of two melphalan protocols and evaluation of outcome and prognostic factors in multiple myeloma in dogs

PubMed Central

Fernández, Ricardo

2018-01-01

Background Multiple myeloma (MM) in dogs typically is treated with melphalan. A daily melphalan dosing schedule reportedly is well tolerated and associated with favorable outcome. Although anecdotally a pulse dose regimen has resulted in successful responses, little long‐term outcome and safety data is available regarding this dosing regimen for dogs with MM. Hypothesis/objectives (1) To compare outcome and adverse event profiles between pulse dose and daily dose melphalan schedules and (2) to report prognostic factors in dogs with MM treated with melphalan. We hypothesized that both protocols would have similar outcomes and tolerability. Animals Thirty‐eight client‐owned dogs diagnosed with MM receiving pulse dose (n = 17) or daily dose (n = 21) melphalan. Methods Retrospective cohort study assessing outcome and adverse events in dogs receiving either protocol. Risk factors were evaluated for their prognostic relevance. Results Both regimens were well tolerated and similarly effective, with an overall median survival time of 930 days. Renal disease and neutrophil‐to‐lymphocyte ratio (NLR) were negative prognostic factors, whereas hypercalcemia and osteolytic lesions were not prognostic factors in this study population. Conclusions and Clinical Importance Positive results support the use of either dosing regimen for the treatment of dogs with MM, and renal disease and NLR were negative prognostic factors. Prospective, controlled, and randomized studies are warranted to confirm these findings. PMID:29566439

Vehicle Integrated Prognostic Reasoner (VIPR) 2010 Annual Final Report

NASA Technical Reports Server (NTRS)

Hadden, George D.; Mylaraswamy, Dinkar; Schimmel, Craig; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

2011-01-01

Honeywell's Central Maintenance Computer Function (CMCF) and Aircraft Condition Monitoring Function (ACMF) represent the state-of-the art in integrated vehicle health management (IVHM). Underlying these technologies is a fault propagation modeling system that provides nose-to-tail coverage and root cause diagnostics. The Vehicle Integrated Prognostic Reasoner (VIPR) extends this technology to interpret evidence generated by advanced diagnostic and prognostic monitors provided by component suppliers to detect, isolate, and predict adverse events that affect flight safety. This report describes year one work that included defining the architecture and communication protocols and establishing the user requirements for such a system. Based on these and a set of ConOps scenarios, we designed and implemented a demonstration of communication pathways and associated three-tiered health management architecture. A series of scripted scenarios showed how VIPR would detect adverse events before they escalate as safety incidents through a combination of advanced reasoning and additional aircraft data collected from an aircraft condition monitoring system. Demonstrating VIPR capability for cases recorded in the ASIAS database and cross linking them with historical aircraft data is planned for year two.

Impact of early life adversity on EMG stress reactivity of the trapezius muscle

PubMed Central

Luijcks, Rosan; Vossen, Catherine J.; Roggeveen, Suzanne; van Os, Jim; Hermens, Hermie J.; Lousberg, Richel

2016-01-01

Abstract Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0–11 years) and adolescence (12–17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability. Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies. PMID:27684800

Prognostic and diagnostic impact of fibrinogen, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio on thymic epithelial tumors outcome

PubMed Central

Janik, Stefan; Raunegger, Thomas; Hacker, Philipp; Ghanim, Bahil; Einwallner, Elisa; Müllauer, Leonhard; Schiefer, Ana-Iris; Moser, Julia; Klepetko, Walter; Ankersmit, Hendrik Jan; Moser, Bernhard

2018-01-01

Background Peripheral blood-derived inflammation-based markers, such as Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Fibrinogen have been identified as prognostic markers in various solid malignancies. Here we aimed to investigate the prognostic and diagnostic impact of NLR, PLR, and Fibrinogen in patients with thymic epithelial tumors (TETs). Results Pretreatment Fibrinogen serum concentrations, NLRs and PLRs were highest in patients with TCs and advanced tumor stages. High pretreatment Fibrinogen serum concentration (≥452.5 mg/dL) was significantly associated with worse cause specific survival (CSS; p = 0.001) and freedom from recurrence (FFR; p = 0.043), high NLR (≥4.0) with worse FFR (p = 0.008), and high PLR (≥136.5) with worse CSS (p = 0.032). Longitudinal analysis revealed that compared to patients without tumor recurrence, patients with tumor recurrence had significantly higher NLR (11.8 ± 4.0 vs. 4.70 ± 0.5; p = 0.001) and PLR (410.8 ± 149.1 vs. 228.3 ± 23.7; p = 0.031). Conclusion Overall, Fibrinogen serum concentrations, NLRs, and PLRs were associated with higher tumor stage, more aggressive tumor behavior, recurrence, and worse outcome. Prospective multicenter studies of the diagnostic and prognostic potential of Fibrinogen, NLR, and PLR are warranted. Methods This retrospective analysis included 122 patients with TETs who underwent surgical resection between 1999-2015. Fibrinogen serum concentrations, NLRs, and PLRs were measured in patients preoperatively, postoperatively, and later during follow-up. These markers were analyzed for association with several clinical variables, including tumor stage, tumor subtype, FFR, and CSS and to evaluate their prognostic and diagnostic impact for detecting tumor recurrence. PMID:29774108

Prognostic impact of HPV-associated p16-expression and smoking status on outcomes following radiotherapy for oropharyngeal cancer: The MARCH-HPV project.

PubMed

Lassen, Pernille; Lacas, Benjamin; Pignon, Jean-Pierre; Trotti, Andy; Zackrisson, Bjorn; Zhang, Qiang; Overgaard, Jens; Blanchard, Pierre

2018-01-01

Evaluate the prognostic and predictive impact of HPV-associated p16-expression and assess the combined prognostic impact of p16 and smoking on altered fractionated radiotherapy (AFRT) for oropharyngeal cancer (OPC) within the frames of the update of the Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH). Patients with OPC, known tumor p16-status and smoking history were identified from the MARCH update, resulting in a dataset of 815 patients from four randomized trials (RTOG9003, DAHANCA6&7, RTOG0129, ARTSCAN). Analysis was performed using a Cox model stratified by trial and adjusted on gender, age, T-stage, N-stage, type of radiotherapy fractionation, p16, smoking. Primary endpoint was progression-free survival (PFS). In total, 465 patients (57%) had p16-positive tumors and 350 (43%) p16-negative. Compared to p16-negative, p16-positive patients had significantly better PFS (HR = 0.42 [95% CI: 0.34-0.51], 28.9% absolute increase at 10 years) and OS (HR = 0.40 [0.32-0.49], 32.1% absolute increase at 10 years). No interaction between p16-status and fractionation schedule was detected. Smoking negatively impacted outcome; in the p16-positive subgroup, never smokers had significantly better PFS than former/current smokers (HR = 0.49 [0.33-0.75], 24.2% survival benefit at 10 years). No predictive impact of p16-status on response to AFRT could be detected but the strong prognostic impact of p16-status was confirmed and especially p16-positive never smoking patients have superior outcome after RT. Copyright © 2017 Elsevier B.V. All rights reserved.

Prognostic impact of C-reactive protein/albumin ratio on the overall survival of patients with advanced nonsmall cell lung cancers receiving palliative chemotherapy

PubMed Central

Koh, Young W.; Lee, Hyun W.

2017-01-01

Abstract Recent studies have indicated that the C-reactive protein (CRP)/albumin (CRP/Alb) ratio is associated with clinical outcomes in patients with various carcinomas. However, no studies have explored the association between the ratio of CRP/Alb and clinical outcome of inoperable patients with nonsmall cell lung cancers (NSCLCs). We examined the prognostic impact of CRP/Alb ratio on 165 stage IV NSCLC receiving palliative chemotherapy. The optimal cutoff level of CRP/Alb ratio was set at 0.195. The median follow-up time was 9 months (range, 1–74 months). On univariate analysis, high CRP/Alb ratio (≥0.195) was correlated (P < .001) with poorer overall survival (OS). Subgroup analysis of adenocarcinoma showed that CRP/Alb ratio was significantly (P < .001) associated with OS. Multivariate analysis showed that CRP/Alb ratio was an independent prognostic factor for OS (hazard ratio: 2.227, P = .001). Subgroup analysis revealed that the CRP/Alb ratio had a significant (P = .001) prognostic impact on adenocarcinoma patients receiving platinum chemotherapy. Elevated CRP/Alb ratio was significantly associated with male gender (P = .002) and smoking history (P = .009). The results of this study suggest that the CRP/Alb ratio might be used as a simple, inexpensive, and independent prognostic factor for OS of patients with advanced lung adenocarcinomas receiving platinum chemotherapy. PMID:28489774

Advanced Methods for Determining Prediction Uncertainty in Model-Based Prognostics with Application to Planetary Rovers

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Sankararaman, Shankar

2013-01-01

Prognostics is centered on predicting the time of and time until adverse events in components, subsystems, and systems. It typically involves both a state estimation phase, in which the current health state of a system is identified, and a prediction phase, in which the state is projected forward in time. Since prognostics is mainly a prediction problem, prognostic approaches cannot avoid uncertainty, which arises due to several sources. Prognostics algorithms must both characterize this uncertainty and incorporate it into the predictions so that informed decisions can be made about the system. In this paper, we describe three methods to solve these problems, including Monte Carlo-, unscented transform-, and first-order reliability-based methods. Using a planetary rover as a case study, we demonstrate and compare the different methods in simulation for battery end-of-discharge prediction.

A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients

PubMed Central

Luedi, Markus M.; Singh, Sanjay K.; Mosley, Jennifer C.; Hatami, Masumeh; Gumin, Joy; Sulman, Erik P.; Lang, Frederick F.; Stueber, Frank; Zinn, Pascal O.; Colen, Rivka R.

2016-01-01

Background Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. Methods We utilized three independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in TCGA and REMBRANDT databases. In silico connectivity Map analysis identified camptothecin as antagonist to dexamethasone induced negative effects. Results Pathway analyses predicted an activation of dexamethasone network (z-score:2.908). Top activated canonical pathways included ‘role of BRCA1 in DNA damage response’ (p=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when co-incubated with dexamethasone. Altered cellular functions included cell-movement, cell-survival, and apoptosis with z-scores of 2.815, 5.137, and −3.122 respectively. CEBPB was activated in a dose dependent manner specifically in slow-dividing ‘stem-like’ cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk score had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone effects. Conclusions Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects. PMID:27653222

Characterization and prognostic implication of 17 chromosome abnormalities in myelodysplastic syndrome.

PubMed

Sánchez-Castro, Judit; Marco-Betés, Víctor; Gómez-Arbonés, Xavier; Arenillas, Leonor; Valcarcel, David; Vallespí, Teresa; Costa, Dolors; Nomdedeu, Benet; Jimenez, María José; Granada, Isabel; Grau, Javier; Ardanaz, María T; de la Serna, Javier; Carbonell, Félix; Cervera, José; Sierra, Adriana; Luño, Elisa; Cervero, Carlos J; Falantes, José; Calasanz, María J; González-Porrás, José R; Bailén, Alicia; Amigo, M Luz; Sanz, Guillermo; Solé, Francesc

2013-07-01

The prognosis of chromosome 17 (chr17) abnormalities in patients with primary myelodysplastic syndrome (MDS) remains unclear. The revised International Prognostic Scoring System (IPSS-R) includes these abnormalities within the intermediate cytogenetic risk group. This study assessed the impact on overall survival (OS) and risk of acute myeloid leukemia transformation (AMLt) of chr17 abnormalities in 88 patients with primary MDS. We have compared this group with 1346 patients with primary MDS and abnormal karyotype without chr17 involved. The alterations of chr17 should be considered within group of poor prognosis. The different types of alterations of chromosome 17 behave different prognosis. The study confirms the intermediate prognostic impact of the i(17q), as stated in IPSS-R. The results of the study, however, provide valuable new information on the prognostic impact of alterations of chromosome 17 in complex karyotypes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Did intense adverse media publicity impact on prescribing of paroxetine and the notification of suspected adverse drug reactions? Analysis of routine databases, 2001-2004.

PubMed

Martin, Richard M; May, Margaret; Gunnell, David

2006-02-01

To document the impact on clinical practice in England of media attention around possible adverse effects of paroxetine. Analysis of national selective serotonin reuptake inhibitor (SSRI) prescribing trends and yellow-card adverse drug reaction reports, 2001-2004. From a steady state in 2001, paroxetine prescribing declined sharply from April 2002, coinciding with a USA regulatory action; the subsequent decline in paroxetine prescribing was 1.87% per month (95% confidence interval - 2.06, -1.68). Other SSRI prescribing increased by 1% per month until a major UK review of SSRIs in children in December 2003, after which prescribing plateaued. Media publicity was associated with short-term peaks in yellow-card reports related to paroxetine. Falls in paroxetine and other SSRI prescribing in the UK coincided, respectively, with regulatory communications from the USA and the UK, but associations may have noncausal or other explanations. Reports of adverse reactions to paroxetine appeared to increase after adverse media publicity about the drug.

[Assessing the economic impact of adverse events in Spanish hospitals by using administrative data].

PubMed

Allué, Natalia; Chiarello, Pietro; Bernal Delgado, Enrique; Castells, Xavier; Giraldo, Priscila; Martínez, Natalia; Sarsanedas, Eugenia; Cots, Francesc

2014-01-01

To evaluate the incidence and costs of adverse events registered in an administrative dataset in Spanish hospitals from 2008 to 2010. A retrospective study was carried out that estimated the incremental cost per episode, depending on the presence of adverse events. Costs were obtained from the database of the Spanish Network of Hospital Costs. This database contains data from 12 hospitals that have costs per patient records based on activities and clinical records. Adverse events were identified through the Patient Safety Indicators (validated in the Spanish Health System) created by the Agency for Healthcare Research and Quality together with indicators of the EuroDRG European project. This study included 245,320 episodes with a total cost of 1,308,791,871€. Approximately 17,000 patients (6.8%) experienced an adverse event, representing 16.2% of the total cost. Adverse events, adjusted by diagnosis-related groups, added a mean incremental cost of between €5,260 and €11,905. Six of the 10 adverse events with the highest incremental cost were related to surgical interventions. The total incremental cost of adverse events was € 88,268,906, amounting to an additional 6.7% of total health expenditure. Assessment of the impact of adverse events revealed that these episodes represent significant costs that could be reduced by improving the quality and safety of the Spanish Health System. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Prognostic roles of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in ovarian cancer: a meta-analysis of retrospective studies.

PubMed

Zhao, Zhe; Zhao, Xinrui; Lu, Jingjing; Xue, Jing; Liu, Peishu; Mao, Hongluan

2018-04-01

The systemic inflammatory response markers have been reported to be associated with the prognosis of various cancers. We conducted this meta-analysis of retrospective studies to evaluate and identify the prognostic impact of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) on ovarian cancer. PubMed, EMBASE, and China National Knowledge Infrastructure databases were included to search for eligible studies. The following terms were used: "neutrophil to lymphocyte ratio", "NLR", "platelet to lymphocyte ratio", "PLR", "ovarian cancer", "ovary cancer", "ovarian carcinoma", "ovary carcinoma", "ovarian neoplasm", "ovary neoplasm", "ovarian tumor", and "ovary tumor". The random-effects model was chosen to estimate the pooled HR with 95% CI. Heterogeneity between studies was assessed by Higgins I 2 value. The stability and heterogeneity of studies were analyzed by sensitivity analysis. Publication bias was examined by Egger's test and Begg's test with the funnel plots. 13 studies consisting of 3467 patients were considered for meta-analysis. We found that the high NLR had a poor prognostic impact on OS and PFS in ovarian cancer, with a pooled HR 1.70, 95% CI 1.35-2.15 and HR 1.77, 95% CI 1.48-2.12, respectively. Similarly, the results showed the high PLR adversely affected OS and PFS in ovarian cancer, with a pooled HR 2.05, 95% CI 1.70-2.48 and HR 1.85, 95% CI 1.53-2.25, respectively. In conclusion, we found that both NLR and PLR had an unfavorable impact on PFS and OS of patients with ovarian cancer. Our meta-analysis supported that NLR/PLR could be effective prognostic predictors of ovarian cancer.

Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival.

PubMed

Koen Talsma, A; Shapiro, Joel; Looman, Caspar W N; van Hagen, Pieter; Steyerberg, Ewout W; van der Gaast, Ate; van Berge Henegouwen, Mark I; Wijnhoven, Bas P L; van Lanschot, J Jan B; Hulshof, Maarten C C M; van Laarhoven, Hanneke W M; Nieuwenhuijzen, Grard A P; Hospers, Geke A P; Bonenkamp, Johannes J; Cuesta, Miguel A; Blaisse, Reinoud J B; Busch, Olivier R C; ten Kate, Fiebo J W; Creemers, Geert-Jan; Punt, Cornelis J A; Plukker, John T M; Verheul, Henk M W; van Dekken, Herman; van der Sangen, Maurice J C; Rozema, Tom; Biermann, Katharina; Beukema, Jannet C; Piet, Anna H M; van Rij, Caroline M; Reinders, Janny G; Tilanus, Hugo W

2014-11-01

We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98). The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

Keeping data continuous when analyzing the prognostic impact of a tumor marker: an example with cathepsin D in breast cancer.

PubMed

Bossard, N; Descotes, F; Bremond, A G; Bobin, Y; De Saint Hilaire, P; Golfier, F; Awada, A; Mathevet, P M; Berrerd, L; Barbier, Y; Estève, J

2003-11-01

The prognostic value of cathepsin D has been recently recognized, but as many quantitative tumor markers, its clinical use remains unclear partly because of methodological issues in defining cut-off values. Guidelines have been proposed for analyzing quantitative prognostic factors, underlining the need for keeping data continuous, instead of categorizing them. Flexible approaches, parametric and non-parametric, have been proposed in order to improve the knowledge of the functional form relating a continuous factor to the risk. We studied the prognostic value of cathepsin D in a retrospective hospital cohort of 771 patients with breast cancer, and focused our overall survival analysis, based on the Cox regression, on two flexible approaches: smoothing splines and fractional polynomials. We also determined a cut-off value from the maximum likelihood estimate of a threshold model. These different approaches complemented each other for (1) identifying the functional form relating cathepsin D to the risk, and obtaining a cut-off value and (2) optimizing the adjustment for complex covariate like age at diagnosis in the final multivariate Cox model. We found a significant increase in the death rate, reaching 70% with a doubling of the level of cathepsin D, after the threshold of 37.5 pmol mg(-1). The proper prognostic impact of this marker could be confirmed and a methodology providing appropriate ways to use markers in clinical practice was proposed.

Prognostic importance of DNA ploidy in non-endometrioid, high-risk endometrial carcinomas.

PubMed

Sorbe, Bengt

2016-03-01

The present study investigated the predictive and prognostic impact of DNA ploidy together with other well-known prognostic factors in a series of non-endometrioid, high-risk endometrial carcinomas. From a complete consecutive series of 4,543 endometrial carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stages I-IV, 94 serous carcinomas, 48 clear cell carcinomas and 231 carcinosarcomas were selected as a non-endometrioid, high-risk group for further studies regarding prognosis. The impact of DNA ploidy, as assessed by flow cytometry, was of particular focus. The age of the patients, FIGO stage, depth of myometrial infiltration and tumor expression of p53 were also included in the analyses (univariate and multivariate). In the complete series of cases, the recurrence rate was 37%, and the 5-year overall survival rate was 39% with no difference between the three histological subtypes. The primary cure rate (78%) was also similar for all tumor types studied. DNA ploidy was a significant predictive factor (on univariate analysis) for primary tumor cure rate, and a prognostic factor for survival rate (on univariate and multivariate analyses). The predictive and prognostic impact of DNA ploidy was higher in carcinosarcomas than in serous and clear cell carcinomas. In the majority of multivariate analyses, FIGO stage and depth of myometrial infiltration were the most important predictive (tumor recurrence) and prognostic (survival rate) factors. DNA ploidy status is a less important predictive and prognostic factor in non-endometrioid, high-risk endometrial carcinomas than in the common endometrioid carcinomas, in which FIGO and nuclear grade also are highly significant and important factors.

Homoarginine—A prognostic indicator in adolescents and adults with complex congenital heart disease?

PubMed Central

Mueller, Marieke; Meinitzer, Andreas; Maerz, Winfried; Dschietzig, Thomas

2017-01-01

Background Homoarginine (hArg) has been shown to be of prognostic value in patients with chronic left heart failure. The present study aims to assess the clinical utility and prognostic value of hArg levels in patients with complex congenital heart disease (CHD). Methods Plasma hArg levels were measured in 143 patients with complex CHD and compared to clinical status, echocardiographic and laboratory parameters as well as the occurrence of adverse cardiac events. Results Median hArg levels were 1.5 μmol/l in CHD patients as compared to 1.70 μmol/l in healthy controls (p = 0.051). Median hArg levels were lowest in patients with Fontan palliation (1.27 μmol/l) and Eisenmenger physiology (0.99 μmol/l) and decreased with the severity of adverse cardiac events with lowest values found in patients prior to death or overt heart failure (0.89 μmol/l). According to ROC analysis, the most important predictors of adverse cardiac events were hArg levels (AUC 0.837, p<0.001, CI 0.726–0.947), NYHA class (AUC 0.800, p<0.001, CI 0.672–0.928) and NT-proBNP levels (AUC 0.780, p<0.001, CI 0.669–0.891). The occurrence of overt heart failure or death due to progressive heart failure were best predicted by NYHA class (AUC 0.945, p<0.001, CI 0.898–0.992), hArg levels (AUC 0.911, p<0.001, CI 0.850–0.971) and NT-proBNP levels (AUC 0.877, p<0.001, CI 0.791–0.962), respectively. Conclusion In patients with complex CHD, hArg levels can predict adverse cardiac events as reliably as or even better than NT-proBNP levels and thus might be of prognostic value in this subset of patients. PMID:28886170

Prognostic Value of Right Ventricular Dysfunction Markers for Serious Adverse Events in Acute Normotensive Pulmonary Embolism.

PubMed

Weekes, Anthony J; Johnson, Angela K; Troha, Daniel; Thacker, Gregory; Chanler-Berat, Jordan; Runyon, Michael

2017-02-01

Right ventricular dysfunction (RVD) in pulmonary embolism (PE) has been associated with increased morbidity. Tools for RVD identification are not well defined. The prognostic value of RVD markers to predict serious adverse events (SAE) during hospitalization is unclear. Prospectively compare the incidence of SAE in normotensive emergency department patients with PE based upon RVD by goal-directed echocardiography (GDE), cardiac biomarkers, and right-to-left ventricle ratio by computed tomography (CT). Simplified Pulmonary Embolism Severity Index (sPESI) was calculated. Deaths and readmissions within 30 days were recorded. Consecutive normotensive PE patients underwent GDE focused on RVD (RV enlargement, hypokinesis, or septal bowing), serum troponin, and brain natriuretic peptide (BNP), and evaluation of the CT ventricle ratio. In-hospital SAE and complications within 30 days were recorded. We enrolled 123 normotensive PE patients (median age 59 years, 49% female). Twenty-six of 123 (26%) patients had one or more SAE. RVD was detected in 26% by GDE, in 39% by biomarkers, and in 38% with CT. In-hospital SAE included one death, six respiratory interventions, six dysrhythmias, three major bleeding episodes, and 21 hypotension episodes. Forty-one percent of patients RVD positive by GDE had SAE, compared to the 18% RVD negative by GDE. Odds ratios for GDE, CT, BNP, troponin, and sPESI for SAE were 3.2 (95% confidence interval [CI] 1.2-8.5), 2.0 (95% CI 0.8-5.1), 3.3 (95% CI 1.3-8.6), 4.2 (95% CI 1.4-13.5), and 2.9 (95% CI 1.1-8.3), respectively. Five patients had non-PE-related deaths within 30 days. The incidence of SAE within days of PE was significant in our cohort. Those with RVD had an increased risk of nonmortality SAE. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel H-FABP assay and a fast prognostic score for risk assessment of normotensive pulmonary embolism.

PubMed

Dellas, Claudia; Tschepe, Merle; Seeber, Valerie; Zwiener, Isabella; Kuhnert, Katherina; Schäfer, Katrin; Hasenfuß, Gerd; Konstantinides, Stavros; Lankeit, Mareike

2014-05-05

We tested whether heart-type fatty acid binding protein (H-FABP) measured by a fully-automated immunoturbidimetric assay in comparison to ELISA provides additive prognostic value in patients with pulmonary embolism (PE), and validated a fast prognostic score in comparison to the ESC risk prediction model and the simplified Pulmonary Embolism Severity Index (sPESI). We prospectively examined 271 normotensive patients with PE; of those, 20 (7%) had an adverse 30-day outcome. H-FABP levels determined by immunoturbidimetry were higher (median, 5.2 [IQR; 2.7-9.8] ng/ml) than those by ELISA (2.9 [1.1-5.4] ng/ml), but Bland-Altman plot demonstrated a good agreement of both assays. The area under the curve for H-FABP was greater for immunoturbidimetry than for ELISA (0.82 [0.74-0.91] vs 0.78 [0.68-0.89]; P=0.039). H-FABP measured by immunoturbidimetry (but not by ELISA) provided additive prognostic information to other predictors of 30-day outcome (OR, 12.4 [95% CI, 1.6-97.6]; P=0.017). When H-FABP determined by immunoturbidimetry was integrated into a novel prognostic score (H-FABP, Syncope, and Tachycardia; FAST score), the score provided additive prognostic information by multivariable analysis (OR, 14.2 [3.9-51.4]; p<0.001; c-index, 0.86) which were superior to information obtained by the ESC model (c-index, 0.62; net reclassification improvement (NRI), 0.39 [0.21-0.56]; P<0.001) or the sPESI (c-index, 0.68; NRI, 0.24 [0.05-0.43]; P=0.012). In conclusion, determination of H-FABP by immunoturbidimetry provides prognostic information superior to that of ELISA and, if integrated in the FAST score, appears more suitable to identify patients with an adverse 30-day outcome compared to the ESC model and sPESI.

Recruitment efforts to reduce adverse impact: targeted recruiting for personality, cognitive ability, and diversity.

PubMed

Newman, Daniel A; Lyon, Julie S

2009-03-01

Noting the presumed tradeoff between diversity and performance goals in contemporary selection practice, the authors elaborate on recruiting-based methods for avoiding adverse impact while maintaining aggregate individual productivity. To extend earlier work on the primacy of applicant pool characteristics for resolving adverse impact, they illustrate the advantages of simultaneous cognitive ability- and personality-based recruiting. Results of an algebraic recruiting model support general recruiting for cognitive ability, combined with recruiting for conscientiousness within the underrepresented group. For realistic recruiting effect sizes, this type of recruiting strategy greatly increases average performance of hires and percentage of hires from the underrepresented group. Further results from a policy-capturing study provide initial guidance on how features of organizational image can attract applicants with particular job-related personalities and abilities, in addition to attracting applicants on the basis of demographic background. (c) 2009 APA, all rights reserved.

Lack of Prognostic Impact of Adjuvant Radiation on Oncologic Outcomes in Elderly Women with Breast Cancer.

PubMed

Omidvari, Shapour; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Moaddabshoar, Leila; Dayani, Maliheh; Mosalaei, Ahmad; Ahmadloo, Niloofar; Ansari, Mansour; Mohammadianpanah, Mohammad

2015-01-01

Radiotherapy plays an important role as adjuvant treatment in locally advanced breast cancer and in those patients who have undergone breast-conserving surgery. This study aimed to investigate the prognostic impact of adjuvant radiation on oncologic outcomes in elderly women with breast cancer. In this retrospective study, we reviewed and analyzed the characteristics, treatment outcome and survival of elderly women (aged ≥ 60 years) with breast cancer who were treated and followed-up between 1993 and 2014. The median follow up for the surviving patients was 38 (range 3-207) months. One hundred and seventy-eight patients with a median age of 74 (range 60-95) years were enrolled in the study. Of the total, 60 patients received postoperative adjuvant radiation (radiation group) and the remaining 118 did not (control group). Patients in the radiation group were significantly younger than those in the control group (P value=0.004). In addition, patients in radiation group had higher node stage (P value<0.001) and disease stage (P=0.003) and tended to have higher tumor grade (P=0.031) and received more frequent (P value <0.001) adjuvant and neoadjuvant chemotherapy compared to those in the control group. There was no statistically significant difference between two groups regarding the local control, disease-free survival and overall survival rates. In this study, we did not find a prognostic impact for adjuvant radiation on oncologic outcomes in elderly women with breast cancer.

A Novel Independent Survival Predictor in Pulmonary Embolism: Prognostic Nutritional Index.

PubMed

Hayıroğlu, Mert İlker; Keskin, Muhammed; Keskin, Taha; Uzun, Ahmet Okan; Altay, Servet; Kaya, Adnan; Öz, Ahmet; Çinier, Göksel; Güvenç, Tolga Sinan; Kozan, Ömer

2018-05-01

The prognostic impact of nutritional status in patients with pulmonary embolism (PE) is poorly understood. A well-accepted nutritional status parameter, prognostic nutritional index (PNI), which was first demonstrated to be valuable in patients with cancer and gastrointestinal surgery, was introduced to patients with PE. Our aim was to evaluate the predictive value of PNI in outcomes of patients with PE. We evaluated the in-hospital and long-term (53.8 ± 5.4 months) prognostic impact of PNI on 251 patients with PE. During a median follow-up of 53.8 ± 5.4 months, 27 (11.6%) patients died in hospital course and 31 (13.4%) died in out-of-hospital course. The patients with lower PNI had significantly higher in-hospital and long-term mortality. The Cox proportional hazard analyses showed that PNI was associated with an increased risk of all-cause death for both unadjusted model and adjusted for all covariates. Our study demonstrated that PNI, calculated based on serum albumin level and lymphocyte count, is an independent prognostic factor for mortality in patients with PE.

Combined prognostic value of pretreatment anemia and cervical node necrosis in patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: A large-scale retrospective study.

PubMed

Zhang, Lu-Lu; Zhou, Guan-Qun; Li, Yi-Yang; Tang, Ling-Long; Mao, Yan-Ping; Lin, Ai-Hua; Ma, Jun; Qi, Zhen-Yu; Sun, Ying

2017-12-01

This study investigated the combined prognostic value of pretreatment anemia and cervical node necrosis (CNN) in patients with nasopharyngeal carcinoma (NPC). Retrospective review of 1302 patients with newly diagnosed nonmetastatic NPC treated with intensity-modulated radiotherapy (IMRT) ± chemotherapy. Patients were classified into four groups according to anemia and CNN status. Survival was compared using the log-rank test. Independent prognostic factors were identified using the Cox proportional hazards model. The primary end-point was overall survival (OS); secondary end-points were disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS). Pretreatment anemia was an independent, adverse prognostic factor for DMFS; pretreatment CNN was an independent adverse prognostic factor for all end-points. Five-year survival for non-anemia and non-CNN, anemia, CNN, and anemia and CNN groups were: OS (93.1%, 87.2%, 82.9%, 76.3%, P < 0.001), DFS (87.0%, 84.0%, 73.9%, 64.6%, P < 0.001), DMFS (94.1%, 92.1%, 82.4%, 72.5%, P < 0.001), and LRRFS (92.8%, 92.4%, 88.7%, 84.0%, P = 0.012). The non-anemia and non-CNN group had best survival outcomes; anemia and CNN group, the poorest. Multivariate analysis demonstrated combined anemia and CNN was an independent prognostic factor for OS, DFS, DMFS, and LRRFS (P < 0.05). The combination of anemia and CNN is an independent adverse prognostic factor in patients with NPC treated using IMRT ± chemotherapy. Assessment of pretreatment anemia and CNN improved risk stratification, especially for patients with anemia and CNN who have poorest prognosis. This study may aid the design of individualized treatment plans to improve treatment outcomes. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Prognostic Implications of Monosomies in Patients With Multiple Myeloma.

PubMed

Shin, Sang-Yong; Eom, Hyeon-Seok; Sohn, Ji Yeon; Lee, Hyewon; Park, Boram; Joo, Jungnam; Jang, Ja-Hyun; Lee, Mi-Na; Kim, Jung Kwon; Kong, Sun-Young

2017-03-01

Cytogenetic analysis aides in risk stratification for patients with multiple myeloma (MM). Although several cytogenetic aberrations have been reported to be prognostic, less is known about the association between the presence of monosomies and prognosis. The present study evaluated the prevalence and prognostic implications of monosomies in patients with MM. Karyotypes were determined using conventional cytogenetics and fluorescence in situ hybridization (FISH). The prognostic effect of monosomies was evaluated by comparison with the clinical factors in MM patients with normal karyotypes. Karyotypes were successfully determined in 167 of the 170 patients with MM. Of these 167 patients, 52 (31.1%) had abnormal karyotypes. Univariable analyses showed that a normal karyotype, hypodiploidy, monosomies of chromosomes 13 and 16, deletion or monosomy of 13q14, and loss of X detected by metaphase analysis were each associated with reduced progression-free survival (P < .05 for each). Univariable analyses showed that a normal karyotype, hypodiploidy, monosomies of chromosomes 13 and 16, deletion or monosomy of 13q14 detected by metaphase analysis and FISH-determined RB1 (13q)/TP53 (17p) deletion were each associated with reduced overall survival (P < .05 for each). Multivariable analysis showed that hypodiploidy detected by metaphase analysis was independently prognostic of shorter progression-free survival (P < .05 for each) and that hypodiploidy, monosomy 16, and loss of Y chromosome and FISH-determined TP53 (17p) deletion were associated with reduced overall survival (P < .05 for each). In addition to known cytogenetic abnormalities, such as monosomy 13, hypodiploidy, and TP53 (17p) deletion, monosomy 16 and loss of the Y chromosome have adverse prognostic implications in patients with MM. Copyright © 2016 Elsevier Inc. All rights reserved.

[Prognostic impact of Helicobacter pylori infection and eradication therapy in gastric mucosa-associated lymphoid tissue lymphoma].

PubMed

Park, Sang Hyuk; Chi, Hyun-Sook; Park, Seo-Jin; Jang, Seongsoo; Park, Chan-Jeoung; Huh, Joo Ryung

2010-12-01

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is associated with Helicobacter pylori infection and H. pylori eradication is used as its first-line therapy. However, controversies exist about the prognostic value of H. pylori infection in these patients. We evaluated the prognostic impact of H. pylori infection and eradication therapy in gastric MALT lymphoma. A total of 292 patients diagnosed with MALT lymphoma since 2000 were analysed. MALT lymphoma was diagnosed with tissue biopsy and H. pylori infection was diagnosed with hematoxylin-eosin and additional Warthin-Starry stains on tissue sections. Clinical variables such as bone marrow (BM) involvement, multiorgan involvement, tumor stage at diagnosis, and remission were obtained with retrospective review of electronic medical records. Non-gastric MALT lymphoma patients showed higher multiorgan involvement rates (26.6% vs. 9.6%, P<0.001) and higher proportion of stage ≥ 3 (27.7% vs. 16.7%, P=0.029) than gastric cases. Regarding gastric MALT lymphoma, patients with H. pylori infection at diagnosis showed significantly less BM (2.1% vs. 21.8%, P<0.001) and multiorgan involvement rates (6.3% vs. 18.2%, P=0.011) than those without infection. But there was no significant difference in remission rates between them. In contrast, those with successful H. pylori eradication therapy showed significantly higher remission rates (81.0% vs. 30.8%, P<0.001) than those with failure. Non-gastric MALT lymphoma patients showed worse prognosis compared to gastric cases. As for remission rates in patients with gastric MALT lymphoma, successful H. pylori eradication therapy could be a good prognostic factor even if H. pylori infection was present at diagnosis.

Prognostic factors of pathologic stage IB non-small cell lung cancer.

PubMed

Yano, Motoki; Sasaki, Hidefumi; Moriyama, Satoru; Kawano, Osamu; Hikosaka, Yu; Fujii, Yoshitaka

2011-01-01

In pathologic IB (pIB) non-small cell lung cancer, especially in adenocarcinoma, adjuvant chemotherapy with uracil-tegafur is widely recognized as being effective. The aim of this study was to determine the prognostic factors of pIB disease. Sixty patients who were diagnosed with pIB disease between 2004 and 2007 were retrospectively analyzed. Of 60 patients, 22 (36.7%) opted for surgery plus adjuvant chemotherapy with uracil-tegafur, whereas 38 (63.3%) opted for surgery only. The oral administration dose of uracil-tegafur was 400 mg/body. Compliance of adjuvant chemotherapy with uracil-tegafur was 65.5% in 12 months, 57.3% in 24 months. Adjuvant chemotherapy was interrupted in 11 patients because of the recurrence of disease in 3 patients and adverse reaction in 8 patients. Anorexia was the most common adverse reaction. The larger tumor diameter (5 cm<) and p2 pleural invasion were the worse prognostic factors in disease free survival in a univariate analysis and a multivariate analysis (hazard ratio = 0.26 and 0.25; p = 0.028 and 0.032, respectively). The prognosis of the patients with pleural invasion and a tumor diameter >5 cm was poor, and these, partly support the forthcoming classification.

Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms

PubMed Central

Carstens, Keri; Cayabyab, Bonifacio; De Schrijver, Adinda; Gadaleta, Patricia G; Hellmich, Richard L; Romeis, Jörg; Storer, Nicholas; Valicente, Fernando H; Wach, Michael

2014-01-01

Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs are assessed using surrogate species, and it is critical that the data derived from surrogates accurately predict any adverse impacts likely to be observed from the use of the crop in the agricultural context. The key is to select surrogate species that best represent the valued NTOs in the location where the crop is going to be introduced, but this selection process poses numerous challenges for the developers of GE crops who will perform the tests, as well as for the ecologists and regulators who will interpret the test results. These issues were the subject of a conference “Surrogate Species Selection for Assessing Potential Adverse Environmental Impacts of Genetically Engineered Plants on Non-Target Organisms” convened by the Center for Environmental Risk Assessment, ILSI Research Foundation. This report summarizes the proceedings of the conference, including the presentations, discussions and the points of consensus agreed to by the participants. PMID:24637519

Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms.

PubMed

Carstens, Keri; Cayabyab, Bonifacio; De Schrijver, Adinda; Gadaleta, Patricia G; Hellmich, Richard L; Romeis, Jörg; Storer, Nicholas; Valicente, Fernando H; Wach, Michael

2014-01-01

Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs are assessed using surrogate species, and it is critical that the data derived from surrogates accurately predict any adverse impacts likely to be observed from the use of the crop in the agricultural context. The key is to select surrogate species that best represent the valued NTOs in the location where the crop is going to be introduced, but this selection process poses numerous challenges for the developers of GE crops who will perform the tests, as well as for the ecologists and regulators who will interpret the test results. These issues were the subject of a conference "Surrogate Species Selection for Assessing Potential Adverse Environmental Impacts of Genetically Engineered Plants on Non-Target Organisms" convened by the Center for Environmental Risk Assessment, ILSI Research Foundation. This report summarizes the proceedings of the conference, including the presentations, discussions and the points of consensus agreed to by the participants.

GPU Accelerated Prognostics

NASA Technical Reports Server (NTRS)

Gorospe, George E., Jr.; Daigle, Matthew J.; Sankararaman, Shankar; Kulkarni, Chetan S.; Ng, Eley

2017-01-01

Prognostic methods enable operators and maintainers to predict the future performance for critical systems. However, these methods can be computationally expensive and may need to be performed each time new information about the system becomes available. In light of these computational requirements, we have investigated the application of graphics processing units (GPUs) as a computational platform for real-time prognostics. Recent advances in GPU technology have reduced cost and increased the computational capability of these highly parallel processing units, making them more attractive for the deployment of prognostic software. We present a survey of model-based prognostic algorithms with considerations for leveraging the parallel architecture of the GPU and a case study of GPU-accelerated battery prognostics with computational performance results.

Prognostics for Microgrid Components

NASA Technical Reports Server (NTRS)

Saxena, Abhinav

2012-01-01

Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

Review and Analysis of Algorithmic Approaches Developed for Prognostics on CMAPSS Dataset

NASA Technical Reports Server (NTRS)

Ramasso, Emannuel; Saxena, Abhinav

2014-01-01

Benchmarking of prognostic algorithms has been challenging due to limited availability of common datasets suitable for prognostics. In an attempt to alleviate this problem several benchmarking datasets have been collected by NASA's prognostic center of excellence and made available to the Prognostics and Health Management (PHM) community to allow evaluation and comparison of prognostics algorithms. Among those datasets are five C-MAPSS datasets that have been extremely popular due to their unique characteristics making them suitable for prognostics. The C-MAPSS datasets pose several challenges that have been tackled by different methods in the PHM literature. In particular, management of high variability due to sensor noise, effects of operating conditions, and presence of multiple simultaneous fault modes are some factors that have great impact on the generalization capabilities of prognostics algorithms. More than 70 publications have used the C-MAPSS datasets for developing data-driven prognostic algorithms. The C-MAPSS datasets are also shown to be well-suited for development of new machine learning and pattern recognition tools for several key preprocessing steps such as feature extraction and selection, failure mode assessment, operating conditions assessment, health status estimation, uncertainty management, and prognostics performance evaluation. This paper summarizes a comprehensive literature review of publications using C-MAPSS datasets and provides guidelines and references to further usage of these datasets in a manner that allows clear and consistent comparison between different approaches.

Prognostic factors in children with acute myeloid leukaemia and excellent response to remission induction therapy.

PubMed

Karol, Seth E; Coustan-Smith, Elaine; Cao, Xueyuan; Shurtleff, Sheila A; Raimondi, Susana C; Choi, John K; Ribeiro, Raul C; Dahl, Gary V; Bowman, William Paul; Taub, Jeffrey W; Degar, Barbara; Leung, Wing; Downing, James R; Pui, Ching-Hon; Rubnitz, Jeffrey E; Campana, Dario; Inaba, Hiroto

2015-01-01

Minimal residual disease (MRD) is a strong prognostic factor in children and adolescents with acute myeloid leukaemia (AML) but nearly one-quarter of patients who achieve MRD-negative status still relapse. The adverse prognostic factors among MRD-negative patients remain unknown. We analysed the AML02 study cohort to identify demographic and genetic prognostic factors. Among the presenting features, certain 11q23 abnormalities, such as t(6;11) and t(10;11), acute megakaryoblastic leukaemia without the t(1;22), and age ≥10 years were associated with inferior outcome in patients who had MRD-negative status after either remission induction I or II. By contrast, those with rearrangement of CBF genes had superior outcome. Our study identifies patient populations for whom close post-remission MRD monitoring to detect and treat emerging relapse and adjustment in treatment intensity might be indicated. © 2014 John Wiley & Sons Ltd.

Proposed methods and endpoints for defining and assessing adverse environmental impact (AEI) on fish communities/populations in Tennessee River reservoirs.

PubMed

Hickman, Gary D; Brown, Mary L

2002-06-07

Two multimetric indices have been developed to help address fish community (reservoir fish assemblage index [RFAI]) and individual population quality (sport fishing index [SFI]) in Tennessee River reservoirs. The RFAI, with characteristics similar to the index of biotic integrity (IBI) used in stream fish community determinations, was developed to monitor the existing condition of resident fish communities. The index, which incorporates standardized electrofishing of littoral areas and experimental gill netting for limnetic bottom-dwelling species, has been used to determine residential fish community response to various anthropogenic impacts in southeastern reservoirs. The SFI is a multimetric index designed to address the quality of the fishery for individual resident sport fish species in a particular lake or reservoir[4]. The SFI incorporates measures of fish population aspects and angler catch and pressure estimates. This paper proposes 70% of the maximum RFAI score and 10% above the average SFI score for individual species as "screening" endpoints for balanced indigenous populations (BIP) or adverse environmental impact (AEI). Endpoints for these indices indicate: (1) communities/populations are obviously balanced indigenous populations (BIP) indicating no adverse environmental impact (AEI), or are "screened out"; (2) communities/populations are considered to be potentially impacted; and (3) where the resident fish community/population should be considered adversely impacted. Suggestions are also made concerning how examination of individual metric scores can help determine the source or cause of the impact.

[Usefulness of scoring risk for adverse outcomes in older patients with the Identification of Seniors at Risk scale and the Triage Risk Screening Tool: a meta-analysis].

PubMed

Rivero-Santana, Amado; Del Pino-Sedeño, Tasmania; Ramallo-Fariña, Yolanda; Vergara, Itziar; Serrano-Aguilar, Pedro

2017-02-01

A considerable proportion of the geriatric population experiences unfavorable outcomes of hospital emergency department care. An assessment of risk for adverse outcomes would facilitate making changes in clinical management by adjusting available resources to needs according to an individual patient's risk. Risk assessment tools are available, but their prognostic precision varies. This systematic review sought to quantify the prognostic precision of 2 geriatric screening and risk assessment tools commonly used in emergency settings for patients at high risk of adverse outcomes (revisits, functional deterioration, readmissions, or death): the Identification of Seniors at Risk (ISAR) scale and the Triage Risk Screening Tool (TRST). We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and SCOPUS, with no date limits, to find relevant studies. Quality was assessed with the QUADAS-2 checklist (for quality assessment of diagnostic accuracy studies). We pooled data for prognostic yield reported for the ISAR and TRST scores for each short- and medium-term outcome using bivariate random-effects modeling. The sensitivity of the ISAR scoring system as a whole ranged between 67% and 99%; specificity fell between 21% and 41%. TRST sensitivity ranged between 52% and 75% and specificity between 39% and 51%.We conclude that the tools currently used to assess risk of adverse outcomes in patients of advanced age attended in hospital emergency departments do not have adequate prognostic precision to be clinically useful.

The prognostic impact of psychotropic drugs in intentional drug overdose.

PubMed

Tournier, M; Grolleau, A; Cougnard, A; Verdoux, H; Molimard, M

2009-03-01

Psychotropic drugs belong to the drugs most frequently involved in intentional drug overdose (IDO). Few studies have explored their prognostic impact during hospitalisation for IDO. In order to assess which types of psychotropic drugs ingested during IDOs were associated with an increased morbidity, a cohort study included 1,974 patients consecutively hospitalised for IDO. IDOs were categorised as serious if associated with one of the following criteria: death, hospitalisation longer than 48 h, respiratory support, vasopressive drugs, cardiac massage or dialysis. Nearly all the patients ingested psychotropic medications during the IDO (88.4%), most often benzodiazepines (71.6%). Serious IDO was associated with tricyclics (OR 5.7; 95% CI 3.3-9.8), lithium (OR 4.3; 95% CI 1.6-11.6), carbamates (OR 2.7; 95% CI 1.8-4), anticonvulsants (OR 2.4: 95% CI 1.4-4.3), first-generation antipsychotics (OR 2.4; 95% CI 1.7-3.5) or selective serotonin reuptake inhibitors (SSRIs) (OR 1.6; 95% CI 1.1-2.3). Some drugs may be dangerous because of low toxic doses; hence, prescriptions of short duration may be recommended. Moreover, for safety reasons, prescribers may prefer SSRIs to tricyclics and benzodiazepines to carbamates or phenothiazines.

Prognostic impact of location and extent of vessel-related ischemia at myocardial perfusion scintigraphy in patients with or at risk for coronary artery disease.

PubMed

Nudi, Francesco; Schillaci, Orazio; Neri, Giandomenico; Pinto, Annamaria; Procaccini, Enrica; Vetere, Maurizio; Frati, Giacomo; Tomai, Fabrizio; Biondi-Zoccai, Giuseppe

2016-04-01

Myocardial perfusion scintigraphy (MPS) has an established diagnostic and prognostic role in patients with or at risk for coronary artery disease, with ischemia severity and extent having already been identified as key predictors. Whether this is affected by the location of myocardial ischemia is uncertain. We aimed at comparing the prognostic outlook of patients undergoing MPS according to the site of ischemia. Our institutional database was queried for subjects undergoing MPS, without myocardial necrosis or recent revascularization. We focused on the prognostic impact of location of vessel-related ischemia (VRI) at MPS, distinguishing four mutually exclusive groups: single-VRI involving left anterior descending (LAD), single-VRI not involving LAD, multi-VRI involving LAD, and multi-VRI not involving LAD. The primary outcome was the long-term (>1 year) rate of death or myocardial infarction (D/MI). A total of 13,254 patients were included. Moderate or severe VRI occurred in 2,627 (20%) patients. Clinical outcomes were significantly different among the groups of patients with moderate or severe VRI, including death, cardiac death, non-fatal myocardial infarction or their composites (overall P < .001). Specifically, and excluding subjects undergoing revascularization as first follow-up event, D/MI occurred in 8.4% of patients with single-VRI involving LAD, 5.5% of subjects with single-VRI not involving LAD, 16.5% of those with multi-VRI involving LAD, and 7.3% of patients with multi-VRI not involving LAD (overall P < .001). Even at incremental multivariable Cox proportional analysis, hierarchical VRI was independently associated with an increased risk of D/MI [hazard ratio = 1.17 (1.04-1.08) for each class increment, P = .010]. Location and extent of myocardial ischemia at MPS according to the VRI concept have a hierarchical predictive impact, with multi-VRI involving LAD being significantly and independently more prognostically ominous than other types of VRI.

TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis.

PubMed

Kulasekararaj, Austin G; Smith, Alexander E; Mian, Syed A; Mohamedali, Azim M; Krishnamurthy, Pramila; Lea, Nicholas C; Gäken, Joop; Pennaneach, Coralie; Ireland, Robin; Czepulkowski, Barbara; Pomplun, Sabine; Marsh, Judith C; Mufti, Ghulam J

2013-03-01

This study aimed to determine the incidence/prognostic impact of TP53 mutation in 318 myelodysplastic syndrome (MDS) patients, and to correlate the changes to cytogenetics, single nucleotide polymorphism array karyotyping and clinical outcome. The median age was 65 years (17-89 years) and median follow-up was 45 months [95% confidence interval (CI) 27-62 months]. TP53 mutations occurred in 30 (9.4%) patients, exclusively in isolated del5q (19%) and complex karyotype (CK) with -5/5q-(72%), correlated with International Prognostic Scoring System intermediate-2/high, TP53 protein expression, higher blast count and leukaemic progression. Patients with mutant TP53 had a paucity of mutations in other genes implicated in myeloid malignancies. Median overall survival of patients with TP53 mutation was shorter than wild-type (9 versus 66 months, P < 0.001) and it retained significance in multivariable model (Hazard Ratio 3.8, 95%CI 2.3-6.3,P < 0.001). None of the sequentially analysed samples showed a disappearance of the mutant clone or emergence of new clones, suggesting an early occurrence of TP53 mutations. A reduction in mutant clone correlated with response to 5-azacitidine, however clones increased in non-responders and persisted at relapse. The adverse impact of TP53 persists after adjustment for cytogenetic risk and is of practical importance in evaluating prognosis. The relatively common occurrence of these mutations in two different prognostic spectrums of MDS, i.e. isolated 5q- and CK with -5/5q-, possibly implies two different mechanistic roles for TP53 protein. © 2013 Crown copyright. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection.

PubMed

Axelsson, Lars; Nyman, Jan; Haugen-Cange, Hedda; Bove, Mogens; Johansson, Leif; De Lara, Shahin; Kovács, Anikó; Hammerlid, Eva

2017-06-10

Head and neck cancer of unknown primary (HNCUP) is rare and prospective studies are lacking. The impact of different prognostic factors such as age and N stage is not completely known, the optimal treatment is not yet established, and the reported survival rates vary. In the last decade, human papilloma virus (HPV) has been identified as a common cause of and important prognostic factor in oropharyngeal cancer, and there is now growing interest in the importance of HPV for HNCUP. The aim of the present study on curatively treated HNCUP was to investigate the prognostic importance of different factors, including HPV status, treatment, and overall survival. A search for HNCUP was performed in the Swedish Cancer Registry, Western health district, between the years 1992-2009. The medical records were reviewed, and only patients with squamous cell carcinoma or undifferentiated carcinoma treated with curative intent were included. The tumor specimens were retrospectively analyzed for HPV with p16 immunostaining. Sixty-eight patients were included. The mean age was 59 years. The majority were males, and had N2 tumors. Sixty-nine percent of the tumors were HPV positive using p16 staining. Patients who were older than 70 years, patients with N3-stage tumors, and patients with tumors that were p16 negative had a significantly worse prognosis. The overall 5-year survival rate for patients with p16-positive tumors was 88% vs 61% for p16-negative tumors. Treatment with neck dissection and postoperative radiation or (chemo) radiation had 81 and 88% 5-year survival rates, respectively. The overall and disease-free 5-year survival rates for all patients in the study were 82 and 74%. Curatively treated HNCUP had good survival. HPV infection was common. Independent prognostic factors for survival were age over 70 years, HPV status and N3 stage. We recommend that HPV analysis should be performed routinely for HNCUP. Treatment with neck dissection and postoperative radiation or

A Holistic Look at Minimizing Adverse Environmental Impact Under Section 316(b) of the Clean Water Act

DOE PAGES

Veil, John A.; Puder, Markus G.; Littleton, Debra J.; ...

2002-01-01

Section 316(b) of the Clean Water Act (CWA) requires that “the location, design, construction, and capacity of cooling water intake structures reflect the best technology available for minimizing adverse environmental impact.” As the U.S. Environmental Protection Agency (EPA) develops new regulations to implement Section 316(b), much of the debate has centered on adverse impingement and entrainment impacts of cooling-water intake structures. Depending on the specific location and intake layout, once-through cooling systems withdrawing many millions of gallons of water per day can, to a varying degree, harm fish and other aquatic organisms in the water bodies from which the coolingmore » water is withdrawn. Therefore, opponents of once-through cooling systems have encouraged the EPA to require wet or dry cooling tower systems as the best technology available (BTA), without considering site-specific conditions. However, within the context of the broader scope of the CWA mandate, this focus seems too narrow. Therefore, this article examines the phrase “minimizing adverse environmental impact” in a holistic light. Emphasis is placed on the analysis of the terms “environmental” and “minimizing.” Congress chose “environmental” in lieu of other more narrowly focused terms like “impingement and entrainment,” “water quality,” or “aquatic life.” In this light, BTA for cooling-water intake structures must minimize the entire suite of environmental impacts, as opposed to just those associated with impingement and entrainment. Wet and dry cooling tower systems work well to minimize entrainment and impingement, but they introduce other equally important impacts because they impose an energy penalty on the power output of the generating unit. The energy penalty results from a reduction in plant operating efficiency and an increase in internal power consumption. As a consequence of the energy penalty, power companies must generate additional

Hypoglycorrhachia in Adults with Community-Acquired Meningitis: Etiologies and Prognostic Significance

PubMed Central

Shrikanth, Vandana; Salazar, Lucrecia; Khoury, Nabil; Wootton, Susan; Hasbun, Rodrigo

2015-01-01

Study objectives Hypoglycorrhachia (CSF glucose < 45mg/dL) has been identified as a prognostic factor in patients with meningitis. We analyzed the differential diagnosis of hypoglycorrhachia and its clinical significance. Methods Retrospective study of 620 adult patients with community acquired meningitis [CSF WBC >5 cells/mm3, absence of a CSF shunt or recent neurosurgical procedure (< 1 month)] at 8 Memorial Hermann Hospitals in Houston, TX from January, 2005 to December, 2010. An adverse clinical outcome was defined as a Glasgow outcome scale of 4 or less. Results Out of 620 patients with meningitis, 116 (19%) had hypoglycorrachia. Etiologies of hypoglycorrhachia were idiopathic (40), bacterial (27), cryptococcal (26), viral (15), and tuberculous (4). Patients with hypoglycorrachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status and focal neurological deficits compared to those patients without hypoglycorrachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions and abnormal cranial imaging (p<005). Furthermore, patients with hypoglycorrachia had more adverse clinical outcomes [26 out of 116 (22.4%) vs. 45 out of 504 (8.9%)] (p< 0.001). Conclusion Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis. PMID:26299186

Assessing planetary and regional nitrogen boundaries related to food security and adverse environmental impacts

NASA Astrophysics Data System (ADS)

de Vries, Wim; Kros, Hans; Kroeze, Carolien; Seitzinger, Sybil

2014-05-01

In this presentation, we first discuss the concept of -, governance interest in- and criticism on planetary boundaries, specifically with respect to the nitrogen (N) cycle. We then systematically evaluate the criticism and argue that planetary N boundaries need to include both the benefits and adverse impacts of reactive N (Nr) and the spatial variability of Nr impacts, in terms of shortage and surplus, being main arguments for not deriving such boundaries. Next, we present an holistic approach for an updated planetary N boundary by considering the need to: (i) avoid adverse impacts of elevated Nr emissions to water, air and soils, and (ii) feed the world population in an adequate way. The derivation of a planetary N boundary, in terms of anthropogenic fixation of di-nitrogen (N2) by growing legumes and production of N fertilizer, is illustrated by (i) identification of multiple threat N indicators and setting critical limits for them, (ii) back calculating critical N losses from critical limits for N indicators, while accounting for the spatial variability of indicators and their exceedance and (iii) back calculating critical N fixation rates from critical N losses. The derivation of the needed planetary N fixation is assessed from the global population, the recommended dietary N consumption per capita and the N use efficiency in the complete chain from N fixation to N consumption. Results of example applications show that the previously suggested planetary N boundary of 25% of the current value is too low in view of needed N fixation and also unnecessary in view of most environmental impacts. We also illustrate the impacts of changes in the N use efficiency on planetary boundaries in terms of critical N fixation rates.

Ductal carcinoma in situ: USC/Van Nuys Prognostic Index and the impact of margin status.

PubMed

Silverstein, Melvin J; Buchanan, Claire

2003-12-01

As our knowledge of ductal carcinoma in situ (DCIS) continues to evolve, treatment decision-making has become increasingly complex and controversial for both patients and physicians. Treatment options include mastectomy, and breast conservation with or without radiation therapy. Data produced from the randomized clinical trials for DCIS has provided the basis for important treatment recommendations, but are not without limitations. In this article, we review our prospectively collected database consisting of 1036 patients with DCIS treated at the Van Nuys Breast Center and the USC/Norris Comprehensive Cancer Center. We review the use of the USC/Van Nuys Prognostic Index, a clinical algorithm designed to assist physicians in selection of appropriate treatments, and examine the impact of margin status as a sole predictor of local recurrence.

Novel recurrent chromosomal aberrations detected in clonal plasma cells of light chain amyloidosis patients show potential adverse prognostic effect: first results from a genome-wide copy number array analysis.

PubMed

Granzow, Martin; Hegenbart, Ute; Hinderhofer, Katrin; Hose, Dirk; Seckinger, Anja; Bochtler, Tilmann; Hemminki, Kari; Goldschmidt, Hartmut; Schönland, Stefan O; Jauch, Anna

2017-07-01

Immunoglobulin light chain (AL) amyloidosis is a rare plasma cell dyscrasia characterized by the deposition of abnormal amyloid fibrils in multiple organs, thus impairing their function. In the largest cohort studied up to now of 118 CD138-purified plasma cell samples from previously untreated immunoglobulin light chain amyloidosis patients, we assessed in parallel copy number alterations using high-density copy number arrays and interphase fluorescence in situ hybridization (iFISH). We used fluorescence in situ hybridization probes for the IgH translocations t(11;14), t(4;14), and t(14;16) or any other IgH rearrangement as well as numerical aberrations of the chromosome loci 1q21, 8p21, 5p15/5q35, 11q22.3 or 11q23, 13q14, 15q22, 17p13, and 19q13. Recurrent gains included chromosomes 1q (36%), 9 (24%), 11q (24%), as well as 19 (15%). Recurrent losses affected chromosome 13 (29% monosomy) and partial losses of 14q (19%), 16q (14%) and 13q (12%), respectively. In 88% of patients with translocation t(11;14), the hallmark chromosomal aberration in AL amyloidosis, a concomitant gain of 11q22.3/11q23 detected by iFISH was part of the unbalanced translocation der(14)t(11;14)(q13;q32) with the breakpoint in the CCND1/MYEOV gene region. Partial loss of chromosome regions 14q and 16q were significantly associated to gain 1q. Gain 1q21 detected by iFISH almost always resulted from a gain of the long arm of chromosome 1 and not from trisomy 1, whereas deletions on chromosome 1p were rarely found. Overall and event-free survival analysis found a potential adverse prognostic effect of concomitant gain 1q and deletion 14q as well as of deletion 1p. In conclusion, in the first whole genome report of clonal plasma cells in AL amyloidosis, novel aberrations and hitherto unknown potential adverse prognostic effects were uncovered. Copyright© 2017 Ferrata Storti Foundation.

Novel recurrent chromosomal aberrations detected in clonal plasma cells of light chain amyloidosis patients show potential adverse prognostic effect: first results from a genome-wide copy number array analysis

PubMed Central

Granzow, Martin; Hegenbart, Ute; Hinderhofer, Katrin; Hose, Dirk; Seckinger, Anja; Bochtler, Tilmann; Hemminki, Kari; Goldschmidt, Hartmut; Schönland, Stefan O.; Jauch, Anna

2017-01-01

Immunoglobulin light chain (AL) amyloidosis is a rare plasma cell dyscrasia characterized by the deposition of abnormal amyloid fibrils in multiple organs, thus impairing their function. In the largest cohort studied up to now of 118 CD138-purified plasma cell samples from previously untreated immunoglobulin light chain amyloidosis patients, we assessed in parallel copy number alterations using high-density copy number arrays and interphase fluorescence in situ hybridization (iFISH). We used fluorescence in situ hybridization probes for the IgH translocations t(11;14), t(4;14), and t(14;16) or any other IgH rearrangement as well as numerical aberrations of the chromosome loci 1q21, 8p21, 5p15/5q35, 11q22.3 or 11q23, 13q14, 15q22, 17p13, and 19q13. Recurrent gains included chromosomes 1q (36%), 9 (24%), 11q (24%), as well as 19 (15%). Recurrent losses affected chromosome 13 (29% monosomy) and partial losses of 14q (19%), 16q (14%) and 13q (12%), respectively. In 88% of patients with translocation t(11;14), the hallmark chromosomal aberration in AL amyloidosis, a concomitant gain of 11q22.3/11q23 detected by iFISH was part of the unbalanced translocation der(14)t(11;14)(q13;q32) with the breakpoint in the CCND1/MYEOV gene region. Partial loss of chromosome regions 14q and 16q were significantly associated to gain 1q. Gain 1q21 detected by iFISH almost always resulted from a gain of the long arm of chromosome 1 and not from trisomy 1, whereas deletions on chromosome 1p were rarely found. Overall and event-free survival analysis found a potential adverse prognostic effect of concomitant gain 1q and deletion 14q as well as of deletion 1p. In conclusion, in the first whole genome report of clonal plasma cells in AL amyloidosis, novel aberrations and hitherto unknown potential adverse prognostic effects were uncovered. PMID:28341732

Adverse childhood experiences: assessing the impact on health and school engagement and the mitigating role of resilience.

PubMed

Bethell, Christina D; Newacheck, Paul; Hawes, Eva; Halfon, Neal

2014-12-01

The ongoing longitudinal Adverse Childhood Experiences Study of adults has found significant associations between chronic conditions; quality of life and life expectancy in adulthood; and the trauma and stress associated with adverse childhood experiences, including physical or emotional abuse or neglect, deprivation, or exposure to violence. Less is known about the population-based epidemiology of adverse childhood experiences among US children. Using the 2011-12 National Survey of Children's Health, we assessed the prevalence of adverse childhood experiences and associations between them and factors affecting children's development and lifelong health. After we adjusted for confounding factors, we found lower rates of school engagement and higher rates of chronic disease among children with adverse childhood experiences. Our findings suggest that building resilience-defined in the survey as "staying calm and in control when faced with a challenge," for children ages 6-17-can ameliorate the negative impact of adverse childhood experiences. We found higher rates of school engagement among children with adverse childhood experiences who demonstrated resilience, as well as higher rates of resilience among children with such experiences who received care in a family-centered medical home. We recommend a coordinated effort to fill knowledge gaps and translate existing knowledge about adverse childhood experiences and resilience into national, state, and local policies, with a focus on addressing childhood trauma in health systems as they evolve during ongoing reform. Project HOPE—The People-to-People Health Foundation, Inc.

Prognostic significance of KIT exon 11 deletion mutation in intermediate-risk gastrointestinal stromal tumor.

PubMed

Quek, Richard; Farid, Mohamad; Kanjanapan, Yada; Lim, Cindy; Tan, Iain Beehuat; Kesavan, Sittampalam; Lim, Tony Kiat Hon; Oon, Lynette Lin-Ean; Goh, Brian Kp; Chan, Weng Hoong; Teo, Melissa; Chung, Alexander Yf; Ong, Hock Soo; Wong, Wai Keong; Tan, Patrick; Yip, Desmond

2017-06-01

Benefit of adjuvant imatinib therapy following curative resection in patients with intermediate-risk gastrointestinal stromal tumor (GIST) is unclear. GIST-specific exon mutations, in particular exon 11 deletions, have been shown to be prognostic. We hypothesize that specific KIT mutations may improve risk stratification in patients with intermediate-risk GIST, identifying a subgroup of patients who may benefit from adjuvant therapy. In total, 142 GIST patients with complete clinicopathologic and mutational data from two sites were included. Risk classification was based on the modified National Institute of Health (NIH) criteria. In this cohort, 74% (n = 105) of patients harbored a KIT mutation; 61% (n = 86) were found in exon 11 of which nearly 70% were KIT exon 11 deletions (n = 60). A total of 18% (n = 25) of cases were classified as having intermediate-risk disease. Univariate analysis confirmed tumor size, mitotic index, nongastric origin, presence of tumor rupture and modified NIH criteria were adversely prognostic for relapse-free survival (RFS). Among KIT/PDGFRA mutants, KIT exon 11 deletions had a significantly worse prognosis (hazard ratio 2.31; 95% confidence interval, 1.30-4.10; P = 0.003). Multivariate analysis confirmed KIT exon 11 deletion (P = 0.003) and clinical risk classification (P < 0.001) as independent adverse prognostic factors for RFS. Intermediate-risk patients harboring KIT exon 11 deletions had RFS outcomes similar to high-risk patients. The presence of KIT exon 11 deletion mutation in patients with intermediate-risk GIST is associated with an inferior clinical outcome with RFS similar to high-risk patients. © 2016 John Wiley & Sons Australia, Ltd.

Diagnostic and Prognostic Stratification in the Emergency Department Using Urinary Biomarkers of Nephron Damage

PubMed Central

Nickolas, Thomas L.; Schmidt-Ott, Kai M.; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J.; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C.; Barasch, Jonathan

2012-01-01

Objectives This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Background Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. Methods In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase–associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. Results All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Conclusion Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. PMID:22240130

The Risk of Adverse Impact in Selections Based on a Test with Known Effect Size

ERIC Educational Resources Information Center

De Corte, Wilfried; Lievens, Filip

2005-01-01

The authors derive the exact sampling distribution function of the adverse impact (AI) ratio for single-stage, top-down selections using tests with known effect sizes. Subsequently, it is shown how this distribution function can be used to determine the risk that a future selection decision on the basis of such tests will result in an outcome that…

Prognostic role of cardiac power index in ambulatory patients with advanced heart failure.

PubMed

Grodin, Justin L; Mullens, Wilfried; Dupont, Matthias; Wu, Yuping; Taylor, David O; Starling, Randall C; Tang, W H Wilson

2015-07-01

Cardiac pump function is often quantified by left ventricular ejection fraction by various imaging modalities. As the heart is commonly conceptualized as a hydraulic pump, cardiac power describes the hydraulic function of the heart. We aim to describe the prognostic value of resting cardiac power index (CPI) in ambulatory patients with advanced heart failure. We calculated CPI in 495 sequential ambulatory patients with advanced heart failure who underwent invasive haemodynamic assessment with longitudinal follow-up of adverse outcomes (all-cause mortality, cardiac transplantation, or ventricular assist device placement). The median CPI was 0.44 W/m(2) (interquartile range 0.37, 0.52). Over a median of 3.3 years, there were 117 deaths, 104 transplants, and 20 ventricular assist device placements in our cohort. Diminished CPI (<0.44 W/m(2) ) was associated with increased adverse outcomes [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.8-3.1, P < 0.0001). The prognostic value of CPI remained significant after adjustment for age, gender, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance, left ventricular ejection fraction, and creatinine [HR 1.5, 95% CI 1.03-2.3, P = 0.04). Furthermore, CPI can risk stratify independently of peak oxygen consumption (HR 2.2, 95% CI 1.4-3.4, P = 0.0003). Resting cardiac power index provides independent and incremental prediction in adverse outcomes beyond traditional haemodynamic and cardio-renal risk factors. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Prognostics for Ground Support Systems: Case Study on Pneumatic Valves

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Goebel, Kai

2011-01-01

Prognostics technologies determine the health (or damage) state of a component or sub-system, and make end of life (EOL) and remaining useful life (RUL) predictions. Such information enables system operators to make informed maintenance decisions and streamline operational and mission-level activities. We develop a model-based prognostics methodology for pneumatic valves used in ground support equipment for cryogenic propellant loading operations. These valves are used to control the flow of propellant, so failures may have a significant impact on launch availability. Therefore, correctly predicting when valves will fail enables timely maintenance that avoids launch delays and aborts. The approach utilizes mathematical models describing the underlying physics of valve degradation, and, employing the particle filtering algorithm for joint state-parameter estimation, determines the health state of the valve and the rate of damage progression, from which EOL and RUL predictions are made. We develop a prototype user interface for valve prognostics, and demonstrate the prognostics approach using historical pneumatic valve data from the Space Shuttle refueling system.

Chronic lymphocytic leukemia: A prognostic model comprising only two biomarkers (IGHV mutational status and FISH cytogenetics) separates patients with different outcome and simplifies the CLL-IPI.

PubMed

Delgado, Julio; Doubek, Michael; Baumann, Tycho; Kotaskova, Jana; Molica, Stefano; Mozas, Pablo; Rivas-Delgado, Alfredo; Morabito, Fortunato; Pospisilova, Sarka; Montserrat, Emili

2017-04-01

Rai and Binet staging systems are important to predict the outcome of patients with chronic lymphocytic leukemia (CLL) but do not reflect the biologic diversity of the disease nor predict response to therapy, which ultimately shape patients' outcome. We devised a biomarkers-only CLL prognostic system based on the two most important prognostic parameters in CLL (i.e., IGHV mutational status and fluorescence in situ hybridization [FISH] cytogenetics), separating three different risk groups: (1) low-risk (mutated IGHV + no adverse FISH cytogenetics [del(17p), del(11q)]); (2) intermediate-risk (either unmutated IGHV or adverse FISH cytogenetics) and (3) high-risk (unmutated IGHV + adverse FISH cytogenetics). In 524 unselected subjects with CLL, the 10-year overall survival was 82% (95% CI 76%-88%), 52% (45%-62%), and 27% (17%-42%) for the low-, intermediate-, and high-risk groups, respectively. Patients with low-risk comprised around 50% of the series and had a life expectancy comparable to the general population. The prognostic model was fully validated in two independent cohorts, including 417 patients representative of general CLL population and 337 patients with Binet stage A CLL. The model had a similar discriminatory value as the CLL-IPI. Moreover, it applied to all patients with CLL independently of age, and separated patients with different risk within Rai or Binet clinical stages. The biomarkers-only CLL prognostic system presented here simplifies the CLL-IPI and could be useful in daily practice and to stratify patients in clinical trials. © 2017 Wiley Periodicals, Inc.

Prognostic impact of interhospital variation in adjuvant chemotherapy for patients with Stage II/III colorectal cancer: a nationwide study.

PubMed

Arakawa, K; Kawai, K; Tanaka, T; Hata, K; Sugihara, K; Nozawa, H

2018-05-12

Clinical guidelines recommend adjuvant chemotherapy for high-risk patients with Stage II-III colorectal cancer. However, chemotherapeutic administration rates differ significantly between hospitals. We assessed the prognostic benefit of adjuvant chemotherapy in patients with Stage IIb/c colorectal cancer, and the prognostic impact of interhospital variations in the administration of adjuvant chemotherapy for Stage II-III colorectal cancer. We conducted a multicentre, retrospective study of 17 757 patients with Stage II-III colorectal cancer treated between 1997 and 2008 in 23 hospitals in Japan. Hospitals were classified as high-rate (rate > 42.8%) or low-rate (rate ≤ 42.8%), chemotherapy prescribing clinics. The 5-year overall survival (OS) of patients with Stage II-III colorectal cancer receiving adjuvant chemotherapy was significantly higher than for those not receiving adjuvant chemotherapy (85.7% vs 79.2%, P < 0.01 and 79.9% vs 72.5%, P < 0.01, respectively). For patients with Stage II disease, adjuvant chemotherapy was an independent factor for longer OS (P < 0.01, hazard ratio = 0.71). Both adjuvant chemotherapy and high-rate hospital independently improved OS for patients with Stage III colorectal cancer (both P < 0.01; hazard ratio = 0.68 and 0.87, respectively). Significant prognostic benefit was found for patients with Stage IIb/c colorectal cancer who received adjuvant chemotherapy, with patients who were treated in hospitals with high adjuvant chemotherapy rates demonstrating better prognoses. Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.

A tool to determine financial impact of adverse events in health care: healthcare quality calculator.

PubMed

Yarbrough, Wendell G; Sewell, Andrew; Tickle, Erin; Rhinehardt, Eric; Harkleroad, Rod; Bennett, Marc; Johnson, Deborah; Wen, Li; Pfeiffer, Matthew; Benegas, Manny; Morath, Julie

2014-12-01

Hospital leaders lack tools to determine the financial impact of poor patient outcomes and adverse events. To provide health-care leaders with decision support for investments to improve care, we created a tool, the Healthcare Quality Calculator (HQCal), which uses institution-specific financial data to calculate impact of poor patient outcomes or quality improvement on present and future margin. Excel and Web-based versions of the HQCal were based on a cohort study framework and created with modular components including major drivers of cost and reimbursement. The Healthcare Quality Calculator (HQCal) compares payment, cost, and profit/loss for patients with and without poor outcomes or quality issues. Cost and payment information for groups with and without quality issues are used by the HQCal to calculate profit or loss. Importantly, institution-specific payment and cost data are used to calculate financial impact and attributable cost associated with poor patient outcomes, adverse events, or quality issues. Because future cost and reimbursement changes can be forecast, the HQCal incorporates a forward-looking component. The flexibility of the HQCal was demonstrated using surgical site infections after abdominal surgery and postoperative surgical airway complications. The Healthcare Quality Calculator determines financial impact of poor patient outcomes and the benefit of initiatives to improve quality. The calculator can identify quality issues that would provide the largest financial benefit if improved; however, it cannot identify specific interventions. The calculator provides a tool to improve transparency regarding both short- and long-term financial consequences of funding, or failing to fund, initiatives to close gaps in quality or improve patient outcomes.

Esophageal luminal stenosis is an independent prognostic factor in esophageal squamous cell carcinoma.

PubMed

Yang, Yu-Shang; Hu, Wei-Peng; Ni, Peng-Zhi; Wang, Wen-Ping; Yuan, Yong; Chen, Long-Qi

2017-06-27

Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC). The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients' overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors. The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036). Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment.

Defining "adverse environmental impact" and making paragraph 316(b) decisions: a fisheries management approach.

PubMed

Bailey, David E; Bulleit, Kristy A N

2002-05-17

The electric utility industry has developed an approach for decisionmaking that includes a definition of Adverse Environmental Impact (AEI) and an implementation process. The definition of AEI is based on lessons from fishery management science and analysis of the statutory term "adverse environmental impact" and is consistent with current natural resource management policy. The industry has proposed a definition focusing on "unacceptable risk to the population"s ability to sustain itself, to support reasonably anticipated commercial or recreational harvests, or to perform its normal ecological function." This definition focuses not on counting individual fish or eggs cropped by the various uses of a water body, but on preserving populations of aquatic organisms and their functions in the aquatic community. The definition recognizes that assessment of AEI should be site-specific and requires both a biological decision and a balancing of diverse societal values. The industry believes that the definition of AEI should be implemented in a process that will maximize the overall societal benefit of the paragraph 316(b) decision by considering the facility"s physical location, design, and operation, as well as the local biology. The approach considers effects on affected fish and shellfish populations and the benefits of any necessary best technology available (BTA) alternatives. This is accomplished through consideration of population impacts, which conversely allows consideration of the benefits of any necessary BTA modifications. This in turn allows selection of BTAs that will protect potentially affected populations in a cost-effective manner. The process also employs risk assessment with stakeholder participation, in accordance with EPA's Guidelines for Ecological Risk Assessment. The information and tools are now available to make informed decisions about site-specific impacts that will ensure protection of aquatic ecosystems and best serve the public interest.

Impact of sex on prognostic host factors in surgical patients with lung cancer.

PubMed

Wainer, Zoe; Wright, Gavin M; Gough, Karla; Daniels, Marissa G; Choong, Peter; Conron, Matthew; Russell, Prudence A; Alam, Naveed Z; Ball, David; Solomon, Benjamin

2017-12-01

Lung cancer has markedly poorer survival in men. Recognized important prognostic factors are divided into host, tumour and environmental factors. Traditional staging systems that use only tumour factors to predict prognosis are of limited accuracy. By examining sex-based patterns of disease-specific survival in non-small cell lung cancer patients, we determined the effect of sex on the prognostic value of additional host factors. Two cohorts of patients treated surgically with curative intent between 2000 and 2009 were utilized. The primary cohort was from Melbourne, Australia, with an independent validation set from the American Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate analyses of validated host-related prognostic factors were performed in both cohorts to investigate the differences in survival between men and women. The Melbourne cohort had 605 patients (61% men) and SEER cohort comprised 55 681 patients (51% men). Disease-specific 5-year survival showed men had statistically significant poorer survival in both cohorts (P < 0.001); Melbourne men at 53.2% compared with women at 68.3%, and SEER 53.3% men and 62.0% women were alive at 5 years. Being male was independently prognostic for disease-specific mortality in the Melbourne cohort after adjustment for ethnicity, smoking history, performance status, age, pathological stage and histology (hazard ratio = 1.54, 95% confidence interval: 1.10-2.16, P = 0.012). Sex differences in non-small cell lung cancer are important irrespective of age, ethnicity, smoking, performance status and tumour, node and metastasis stage. Epidemiological findings such as these should be translated into research and clinical paradigms to determine the factors that influence the survival disadvantage experienced by men. © 2016 Royal Australasian College of Surgeons.

Impact of adverse life events on individuals with low and high schizotypy in a nonpatient sample.

PubMed

Kocsis-Bogár, Krisztina; Miklósi, Mónika; Forintos, Dóra Perczel

2013-03-01

The aims of this study were to gain a better understanding of adverse life events connected with the development of schizotypal personality traits and, also, to examine whether subclinical schizotypy has a relationship with vulnerability to traumatic intrusions and avoidance. In a cross-sectional design, 198 undergraduate students completed the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE), the Impact of Event Scale (IES), and Paykel's Life Events Scale, together with other relevant scales. The number of adverse life events was significantly related to overall schizotypy measured by O-LIFE scores and positive schizotypy measured by the Unusual Experiences (UnEx) subscale. The subjective severity of life events was significantly related to Cognitive Disorganization (CogDis). Measures of positive schizotypy (UnEx and CogDis) were significantly related to the scores on the IES and on the intrusion and avoidance subscales, too. Adverse life events are associated with schizotypal personality traits, which contribute to a tendency for traumatic intrusions, even in a nonpatient sample.

A Generic Software Architecture For Prognostics

NASA Technical Reports Server (NTRS)

Teubert, Christopher; Daigle, Matthew J.; Sankararaman, Shankar; Goebel, Kai; Watkins, Jason

2017-01-01

Prognostics is a systems engineering discipline focused on predicting end-of-life of components and systems. As a relatively new and emerging technology, there are few fielded implementations of prognostics, due in part to practitioners perceiving a large hurdle in developing the models, algorithms, architecture, and integration pieces. As a result, no open software frameworks for applying prognostics currently exist. This paper introduces the Generic Software Architecture for Prognostics (GSAP), an open-source, cross-platform, object-oriented software framework and support library for creating prognostics applications. GSAP was designed to make prognostics more accessible and enable faster adoption and implementation by industry, by reducing the effort and investment required to develop, test, and deploy prognostics. This paper describes the requirements, design, and testing of GSAP. Additionally, a detailed case study involving battery prognostics demonstrates its use.

Impact of childhood adversity on the course and suicidality of depressive disorders: the CRESCEND study.

PubMed

Kim, Sung-Wan; Kang, Hee-Ju; Kim, Seon-Young; Kim, Jae-Min; Yoon, Jin-Sang; Jung, Sung-Won; Lee, Min-Soo; Yim, Hyeon-Woo; Jun, Tae-Youn

2013-10-01

The impact of childhood adversity persists across the life course. This study aimed to investigate the associations of childhood adversity with the course, suicidality, and treatment outcomes of depressive disorders. A total of 919 people with depressive disorders were recruited. Childhood adversities (≤12 years old) were ascertained using a checklist, in sexual abuse, physical abuse by parents, and separation of parents. Various assessment scales were administered at baseline and over 12 weeks of antidepressants treatment. All three forms of childhood adversity were associated with an increased likelihood of experiencing more current stressful events. Scores on the Beck Depression Inventory and Hamilton Anxiety Rating Scale were significantly higher in participants with a history of sexual abuse. Scores on the Beck Depression Inventory, Hamilton Depression Rating Scale, and Perceived Stress Scale were significantly higher, and scores on the WHO Quality of life instrument were significantly lower in participants with a history of physical abuse by parents. They were more likely to receive augmentation and combination treatment after the initial antidepressant treatment, whereas overall response rates to treatment did not differ. Scores on the Beck Scale for suicide ideation were significantly higher after treatment and/or at baseline in patients with sexual or physical abuse. Physical illness was more prevalent in individuals with physical abuse by parents or separation of parents. Depressive patients with a history of childhood adversities had more severe and chronic forms of depression with high suicidality. More intensive treatment with particular clinical attention is indicated for this special population. © 2013 Wiley Periodicals, Inc.

Predicting long-term neurological outcomes after severe traumatic brain injury requiring decompressive craniectomy: A comparison of the CRASH and IMPACT prognostic models.

PubMed

Honeybul, Stephen; Ho, Kwok M

2016-09-01

Predicting long-term neurological outcomes after severe traumatic brain (TBI) is important, but which prognostic model in the context of decompressive craniectomy has the best performance remains uncertain. This prospective observational cohort study included all patients who had severe TBI requiring decompressive craniectomy between 2004 and 2014, in the two neurosurgical centres in Perth, Western Australia. Severe disability, vegetative state, or death were defined as unfavourable neurological outcomes. Area under the receiver-operating-characteristic curve (AUROC) and slope and intercept of the calibration curve were used to assess discrimination and calibration of the CRASH (Corticosteroid-Randomisation-After-Significant-Head injury) and IMPACT (International-Mission-For-Prognosis-And-Clinical-Trial) models, respectively. Of the 319 patients included in the study, 119 (37%) had unfavourable neurological outcomes at 18-month after decompressive craniectomy for severe TBI. Both CRASH (AUROC 0.86, 95% confidence interval 0.81-0.90) and IMPACT full-model (AUROC 0.85, 95% CI 0.80-0.89) were similar in discriminating between favourable and unfavourable neurological outcome at 18-month after surgery (p=0.690 for the difference in AUROC derived from the two models). Although both models tended to over-predict the risks of long-term unfavourable outcome, the IMPACT model had a slightly better calibration than the CRASH model (intercept of the calibration curve=-4.1 vs. -5.7, and log likelihoods -159 vs. -360, respectively), especially when the predicted risks of unfavourable outcome were <80%. Both CRASH and IMPACT prognostic models were good in discriminating between favourable and unfavourable long-term neurological outcome for patients with severe TBI requiring decompressive craniectomy, but the calibration of the IMPACT full-model was better than the CRASH model. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Prognostic impact of peakVO2-changes in stable CHF on chronic beta-blocker treatment.

PubMed

Frankenstein, L; Nelles, M; Hallerbach, M; Dukic, D; Fluegel, A; Schellberg, D; Katus, H A; Remppis, A; Zugck, C

2007-11-15

Peak oxygen uptake (pVO2) is used for risk stratification in chronic heart failure (CHF), but little is known about the prognostic impact of pVO2-changes in patients on chronic beta-blocker (BBL) therapy. We therefore prospectively evaluated individual pVO2-changes at a 6-month interval in patients all receiving BBL. 194 patients with stable CHF on stable medication were included (V1) and underwent clinical evaluation and exercise testing. Testing was repeated (V2) at 5.7+/-1.5 months after V1 and patients were followed >12 months after V2. Death or hospitalisation due to cardiac reasons was the predefined EP (EPP, end-point positive; n=62; EPN, end-point negative; n=113). Initial characteristics did not differ between EPP and EPN. Multivariate cox regression analysis revealed that change of pVO2 (EPP: -0.6+/-2.6 ml/kg min; EPN: +2.5+/-3.3 ml/kg min; p<0.001) was independent to pVO2, LVEF, NTproBNP and NYHA at V2 for prediction of the combined end-point during follow-up. An increase of pVO2 by 10% was identified as an adequate cut-off value for risk stratification and ROC-analysis showed the significant incremental prognostic value of the determination of pVO2 changes in combination with pVO2. Serial measurements of pVO2 yield additional information for risk stratification in clinically homogenous CHF patients receiving BBL. This is the first study demonstrating this fact within a narrow predefined interval with all patients on BBL.

Prognostic impact of number of resected and involved lymph nodes at complete resection on survival in non-small cell lung cancer.

PubMed

Saji, Hisashi; Tsuboi, Masahiro; Yoshida, Koichi; Kato, Yasufumi; Nomura, Masaharu; Matsubayashi, Jun; Nagao, Toshitaka; Kakihana, Masatoshi; Usuda, Jitsuo; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2011-11-01

Lymph node (LN) status is a major determinant of stage and survival in patients with lung cancer. In the 7th edition of the TNM Classification of Malignant Tumors, the number of involved LNs is included in the definition of pN factors in breast, stomach, esophageal, and colorectal cancer, and the pN status significantly correlates with prognosis. We retrospectively investigated the prognostic impact of the number of resected LNs (RLNs) and involved LNs in the context of other established clinical prognostic factors, in a series of 928 consecutive patients with non-small cell lung cancer (NSCLC) who underwent complete resection at our institution between 2000 and 2007. The mean number of RLNs was 15. There was a significant difference in the total number of RLNs categorized between less than 10 and ≥10 (p = 0.0129). Although the incidence of LN involvement was statistically associated with poor prognosis, the largest statistically significant increase in overall survival was observed between 0 to 3 and ≥4 involved LNs (hazard ratio = 7.680; 95% confidence interval = 5.051-11.655, p < 0.0001). On multivariate analysis, we used the ratio between the number of involved LNs and RLNs. The number of RLNs was found to be a strong independent prognostic factor for NSCLC (hazard ratio = 6.803; 95% confidence interval = 4.137-11.186, p < 0.0001). Complete resection including 10 or more LNs influenced survival at complete NSCLC resection. Four involved LNs seemed to be a benchmark for NSCLC prognosis. The number of involved LNs is a strong independent prognostic factor in NSCLC, and the results of this study may provide new information for determining the N category in the next tumor, node, metastasis classification.

A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma.

PubMed

Perry, Anamarija M; Cardesa-Salzmann, Teresa M; Meyer, Paul N; Colomo, Luis; Smith, Lynette M; Fu, Kai; Greiner, Timothy C; Delabie, Jan; Gascoyne, Randy D; Rimsza, Lisa; Jaffe, Elaine S; Ott, German; Rosenwald, Andreas; Braziel, Rita M; Tubbs, Raymond; Cook, James R; Staudt, Louis M; Connors, Joseph M; Sehn, Laurie H; Vose, Julie M; López-Guillermo, Armando; Campo, Elias; Chan, Wing C; Weisenburger, Dennis D

2012-09-13

Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell-like subtype, SPARC (secreted protein, acidic, and rich in cysteine) < 5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies.

Stage Separation Failure: Model Based Diagnostics and Prognostics

NASA Technical Reports Server (NTRS)

Luchinsky, Dmitry; Hafiychuk, Vasyl; Kulikov, Igor; Smelyanskiy, Vadim; Patterson-Hine, Ann; Hanson, John; Hill, Ashley

2010-01-01

Safety of the next-generation space flight vehicles requires development of an in-flight Failure Detection and Prognostic (FD&P) system. Development of such system is challenging task that involves analysis of many hard hitting engineering problems across the board. In this paper we report progress in the development of FD&P for the re-contact fault between upper stage nozzle and the inter-stage caused by the first stage and upper stage separation failure. A high-fidelity models and analytical estimations are applied to analyze the following sequence of events: (i) structural dynamics of the nozzle extension during the impact; (ii) structural stability of the deformed nozzle in the presence of the pressure and temperature loads induced by the hot gas flow during engine start up; and (iii) the fault induced thrust changes in the steady burning regime. The diagnostic is based on the measurements of the impact torque. The prognostic is based on the analysis of the correlation between the actuator signal and fault-induced changes in the nozzle structural stability and thrust.

The Impact of Postnatal Depression and Associated Adversity on Early Mother-Infant Interactions and Later Infant Outcome.

ERIC Educational Resources Information Center

Murray, Lynne; And Others

1996-01-01

Examined the impact of maternal depression and adversity on mother-infant face-to-face interactions at 2 months, and on subsequent infant cognitive development and attachment. Disturbances in early mother-infant interactions were found to be predictive of poorer infant cognitive outcomes at 18 months. (MDM)

Long-term prognostic impact of the attenuated plaque in patients with acute coronary syndrome.

PubMed

Okura, Hiroyuki; Kataoka, Toru; Yoshiyama, Minoru; Yoshikawa, Junichi; Yoshida, Kiyoshi

2016-01-01

Several intravascular ultrasound studies have reported that culprit lesion-attenuated plaque (AP) is related to slow flow/no reflow after percutaneous coronary intervention (PCI). Long-term prognostic impact of the AP is unknown. The aim of this study was to investigate acute and long-term clinical impact of the AP in patients with acute coronary syndrome (ACS). A total of 110 ACS patients who underwent successful PCI were enrolled. Acute and long-term clinical outcomes were compared between patients with AP (AP group: n = 73) and those without AP (non-AP group: n = 37). Long-term cardiac event was defined as a composite of death and ACS. Baseline characteristics in 2 groups were similar. AP was associated with higher TIMI frame count immediately after the first balloon inflation. After thrombectomy and intracoronary drug administration, final TIMI frame count became similar between AP and non-AP group. Although AP was associated with higher incidence of fatal arrhythmia during hospitalization, in-hospital mortality did not differ between the 2 groups. During follow-up (median 6.2 years), cardiac event-free survival did not differ between the 2 groups. Despite the initial unfavorable effect on coronary reflow, presence of AP did not affect acute as well as long-term clinical outcome in patients with ACS.

Clinical and Cost Impact Analysis of a Novel Prognostic Test for Early Detection of Preterm Birth

PubMed Central

Caughey, Aaron B.; Zupancic, John A. F.; Greenberg, James M.; Garfield, Susan S.; Thung, Stephen F.; Iams, Jay D.

2016-01-01

Objective The objective of this study was to evaluate the potential impact to the U.S. health care system by adopting a novel test that identifies women at risk for spontaneous preterm birth. Methods A decision-analytic model was developed to assess clinical and cost outcomes over a 1-year period. The use of a prognostic test to predict spontaneous preterm birth in a hypothetical population of women reflective of the U.S. population (predictive arm) was compared with the current baseline rate of spontaneous preterm birth and associated infant morbidity and mortality (baseline care arm). Results In a population of 3,528,593 births, our model predicts a 23.5% reduction in infant mortality (8,300 vs. 6,343 deaths) with use of the novel test. The rate of acute conditions at birth decreased from 11.2 to 8.1%; similarly, the rate of developmental disabilities decreased from 13.2 to 11.5%. The rate of spontaneous preterm birth decreased from 9.8 to 9.1%, a reduction of 23,430 preterm births. Direct medical costs savings was $511.7M (− 2.1%) in the first year of life. Discussion The use of a prognostic test for reducing spontaneous preterm birth is a dominant strategy that could reduce costs and improve outcomes. More research is needed once such a test is available to determine if these results are borne out upon real-world use. PMID:27917307

Toward IVHM Prognostics

NASA Technical Reports Server (NTRS)

Walsh, Kevin; Venti, Mike

2007-01-01

This viewgraph presentation reviews the prognostics of Integrated Vehicle Health Management. The contents include: 1) Aircraft Operations-Today's way of doing business; 2) Prognostics; 3) NASA's instrumentation data-system rack; 4) Data mining for IVHM; 5) NASA GRC's C-MAPSS generic engine model; and 6) Concluding thoughts.

The two sides of adversity: the effect of distant versus recent adversity on updating emotional content in working memory.

PubMed

Levens, Sara M; Armstrong, Laura Marie; Orejuela-Dávila, Ana I; Alverio, Tabitha

2017-09-01

Previous research suggests that adversity can have both adaptive and maladaptive effects, yet the emotional and working memory processes that contribute to more or less adaptive outcomes are unclear. The present study sought to investigate how updating emotional content differs in adolescents who have experienced past, recent, or no adversity. Participants who had experienced distant adversity (N = 53), no adversity (N = 58), or recent adversity only (N = 20) performed an emotion n-back task with emotional facial expressions. Results revealed that the distant adversity group exhibited significantly faster reaction times (RTs) than the no adversity and recent adversity only groups. In contrast, the recent adversity only group exhibited significantly slower RTs and more errors than the distant adversity and no adversity groups. These results suggest an emotion and executive control pathway by which both the benefits and negative effects of adversity may be conferred. Results also highlight the importance of time in assessing the impact of adversity.

Computational Approaches for Identifying Adverse Outcome Pathways

EPA Science Inventory

Adverse Outcome Pathways (AOPs) provide a framework for organizing toxicity information to improve predictions of the potential adverse impact of environment stressors on humans or wildlife populations, but these benefits are currently limited by the small number of AOPs currentl...

The prognostic impact of tumor volume on stage I non-small cell lung cancer.

PubMed

Su, Xiao-Dong; Xie, Hao-Jun; Liu, Qian-Wen; Mo, Yun-Xian; Long, Hao; Rong, Tie-Hua

2017-02-01

The purpose of this study was to investigate the prognostic impact of tumor volume (TV) on patients with stage I non-small cell lung cancer (NSCLC) after complete resection. We retrospectively reviewed the clinicopathological characteristics of 274 patients with stage I NSCLC who had received preoperative chest computed tomography (CT) scans and complete resection. TV was semi-automatically measured from chest CT scans by using an imaging software program. The optimal cutoff values of TV were determined by X-tile software. Disease-free survival (DFS) and overall survival (OS) were compared using Kaplan-Meier analysis. Univariate and multivariate analyses were performed to identify risk factors for DFS and OS. By using 3.046cm 3 and 8.078cm 3 as two optimal cutoff values of TV, the patients were separated into three groups. The 5-year DFS and OS for patients with TV≤3.046cm 3 , 3.046-8.078cm 3 , and>8.078cm 3 were 88.0%, 73.6%, and 62.1%, respectively (P<0.001), and 91.4%, 84.5%, and 73.3%, respectively (p<0.001). Multivariate analysis showed that age and TV were independent factors associated with DFS. Sex, age, histology, visceral pleural invasion, and TV were independent factors associated with OS. Stage Ia patients might be separated into three groups on the basis of TV with significantly different DFS and OS. Patients with tumor diameter≤2cm and 2-3cm were also stratified into two groups with significantly different DFS and OS on the basis of TV, respectively. TV is an independent risk factor for DFS and OS for stage I NSCLC after complete resection. TV might provide additional prognostic information over tumor diameter in patients with stage I NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Perceptions of quality of life following divorce: a study of children's prognostic thinking.

PubMed

Plunkett, J W; Schaefer, M; Kalter, N; Okla, K; Schreier, S

1986-02-01

The general quality of latency-aged children's prognostic thinking and the way in which they view the long-range impact of divorce upon peer adaptation are explored. When interviewed about responses to two fictional peers with marked behavior problems, 80 children in the third and fifth grades displayed an optimism in their prognostic thinking about the future of these peers. In general, peers from divorced homes were perceived as having a more positive future adjustment than peers from intact homes. However, male subjects from disrupted homes revealed a significantly pessimistic orientation regarding the impact of divorce upon the future; females from disrupted homes had a strikingly optimistic view. Implications for school-based interventions are discussed.

Esophageal luminal stenosis is an independent prognostic factor in esophageal squamous cell carcinoma

PubMed Central

Yang, Yu-Shang; Hu, Wei-Peng; Ni, Peng-Zhi; Wang, Wen-Ping; Yuan, Yong; Chen, Long-Qi

2017-01-01

Background Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC). Methods The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients’ overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors. Results The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036). Conclusions Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment. PMID:28118615

Prognostic grouping of metastatic prostate cancer using conventional pretreatment prognostic factors.

PubMed

Mikkola, Arto; Aro, Jussi; Rannikko, Sakari; Ruutu, Mirja

2009-01-01

To develop three prognostic groups for disease specific mortality based on the binary classified pretreatment variables age, haemoglobin concentration (Hb), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), prostate-specific antigen (PSA), plasma testosterone and estradiol level in hormonally treated patients with metastatic prostate cancer (PCa). The present study comprised 200 Finnprostate 6 study patients, but data on all variables were not known for every patient. The patients were divided into three prognostic risk groups (Rgs) using the prognostically best set of pretreatment variables. The best set was found by backward stepwise selection and the effect of every excluded variable on the binary classification cut-off points of the remaining variables was checked and corrected when needed. The best group of variables was ALP, PSA, ESR and age. All data were known in 142 patients. Patients were given one risk point each for ALP > 180 U/l (normal value 60-275 U/l), PSA > 35 microg/l, ESR > 80 mm/h and age < 60 years. Three risk groups were formed: Rg-a (0-1 risk points), Rg-b (2 risk points) and Rg-c (3-4 risk points). The risk of death from PCa increased statistically significantly with advancing prognostic group. Patients with metastatic PCa can be divided into three statistically significantly different prognostic risk groups for PCa-specific mortality by using the binary classified pretreatment variables ALP, PSA, ESR and age.

Prognostic impact of mRNA levels of osteopontin splice variants in soft tissue sarcoma patients.

PubMed

Hahnel, Antje; Wichmann, Henri; Greither, Thomas; Kappler, Matthias; Würl, Peter; Kotzsch, Matthias; Taubert, Helge; Vordermark, Dirk; Bache, Matthias

2012-04-02

It is well known that osteopontin (OPN) plays an important role in tumor progression and that a high OPN expression level in several tumor entities correlates with poor prognosis in cancer patients. However, little is known about the prognostic relevance of the OPN mRNA splice variants. We analyzed the mRNA expression levels of different OPN splice variants in tumor tissue of 124 soft tissue sarcoma (STS) patients. Quantitative real-time PCR (qRT-PCR) was used to analyze the mRNA expression level of three OPN splice variants (OPN-a, -b and -c). The multivariate Cox's proportional hazard regression model revealed that high mRNA expression levels of OPN splice variants are significantly associated with poor prognosis in STS patients (n = 124). Women (n = 68) with high mRNA expression levels of OPN-a and OPN-b have an especially elevated risk of tumor-related death (OPN-a: RR = 3.0, P = 0.01, CI = 1.3-6.8; OPN-b: RR = 3.4, P = 0.01, CI = 1.4-8.2). In particular, we found that high mRNA expression levels of OPN-b and OPN-c correlated with a high risk of tumor-related death in STS patients that received radiotherapy (n = 52; OPN-b: RR = 10.3, P < 0.01, CI = 2.0-53.7; OPN-c: RR = 11.4, P < 0.01, CI = 2.2-59.3). Our study shows that elevated mRNA expression levels of OPN splice variants are negative prognostic and predictive markers for STS patients. Further studies are needed to clarify the impact of the OPN splice variants on prognosis.

Hypoglycorrhachia in adults with community-acquired meningitis: etiologies and prognostic significance.

PubMed

Shrikanth, Vandana; Salazar, Lucrecia; Khoury, Nabil; Wootton, Susan; Hasbun, Rodrigo

2015-10-01

Hypoglycorrhachia (cerebrospinal fluid (CSF) glucose <45 mg/dl) has been identified as a prognostic factor in patients with meningitis. The differential diagnosis of hypoglycorrhachia and its clinical significance was analyzed in the present study. This was a retrospective study of 620 adult patients with community-acquired meningitis (CSF white blood cell count >5 × 10(6) cells/l and absence of a CSF shunt or recent neurosurgical procedure (<1 month)) at eight Memorial Hermann hospitals in Houston, Texas, from January 2005 to December 2010. An adverse clinical outcome was defined as a Glasgow outcome scale score of ≤ 4. Out of 620 patients with meningitis, 116 (19%) had hypoglycorrhachia. Etiologies of hypoglycorrhachia were idiopathic (n=40), bacterial (n=27), cryptococcal (n=26), viral (n=15), and tuberculous (n=4). Patients with hypoglycorrhachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status, and focal neurological deficits compared to those patients without hypoglycorrhachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions, and abnormal cranial imaging (p<0.05). Furthermore, patients with hypoglycorrhachia had more adverse clinical outcomes (26/116 (22.4%) vs. 45/504 (8.9%); p<0.001). Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The impact of childhood adversity on the persistence of psychotic symptoms: a systematic review and meta-analysis.

PubMed

Trotta, A; Murray, R M; Fisher, H L

2015-01-01

Evidence suggests that childhood adversity is associated with the development of psychotic experiences (PE), psychotic symptoms and disorders. However, less is known regarding the impact of early adversity on the persistence of PE and clinically relevant psychosis. Thus we conducted a systematic review of the association between childhood adversity and the course of PE and symptoms over time. A systematic search of Medline, EMBASE and PsychINFO databases was undertaken to identify articles published between January 1956 and November 2014. We included studies conducted on general population samples, individuals at ultra-high risk (UHR) of psychosis, and patients with full-blown psychotic disorders. A meta-analysis was performed on a subgroup. A total of 20 studies were included. Of these, 17 reported positive associations between exposure to overall or specific subtypes of childhood adversity and persistence of PE or clinically relevant psychotic symptoms. A meta-analysis of nine studies yielded a weighted odds ratio of 1.76 [95% confidence interval (CI) 1.19-2.32, p < 0.001] for general population studies and 1.55 (95% CI 0.32-2.77, p = 0.007) for studies conducted using clinical populations. The available evidence is limited but tentatively suggests that reported exposure to adverse events in childhood is associated with persistence of PE and clinically relevant psychotic symptoms. This partially strengthens the case for addressing the consequences of early adversity in individuals presenting with psychotic phenomena to improve long-term outcomes. However, the heterogeneity of studies was high which urges caution in interpreting the results and highlights the need for more methodologically robust studies.

Prognostic and therapeutic impact of argininosuccinate synthetase 1 control in bladder cancer as monitored longitudinally by PET imaging.

PubMed

Allen, Michael D; Luong, Phuong; Hudson, Chantelle; Leyton, Julius; Delage, Barbara; Ghazaly, Essam; Cutts, Rosalind; Yuan, Ming; Syed, Nelofer; Lo Nigro, Cristiana; Lattanzio, Laura; Chmielewska-Kassassir, Malgorzata; Tomlinson, Ian; Roylance, Rebecca; Whitaker, Hayley C; Warren, Anne Y; Neal, David; Frezza, Christian; Beltran, Luis; Jones, Louise J; Chelala, Claude; Wu, Bor-Wen; Bomalaski, John S; Jackson, Robert C; Lu, Yong-Jie; Crook, Tim; Lemoine, Nicholas R; Mather, Stephen; Foster, Julie; Sosabowski, Jane; Avril, Norbert; Li, Chien-Feng; Szlosarek, Peter W

2014-02-01

Targeted therapies have yet to have significant impact on the survival of patients with bladder cancer. In this study, we focused on the urea cycle enzyme argininosuccinate synthetase 1 (ASS1) as a therapeutic target in bladder cancer, based on our discovery of the prognostic and functional import of ASS1 in this setting. ASS1 expression status in bladder tumors from 183 Caucasian and 295 Asian patients was analyzed, along with its hypothesized prognostic impact and association with clinicopathologic features, including tumor size and invasion. Furthermore, the genetics, biology, and therapeutic implications of ASS1 loss were investigated in urothelial cancer cells. We detected ASS1 negativity in 40% of bladder cancers, in which multivariate analysis indicated worse disease-specific and metastasis-free survival. ASS1 loss secondary to epigenetic silencing was accompanied by increased tumor cell proliferation and invasion, consistent with a tumor-suppressor role for ASS1. In developing a treatment approach, we identified a novel targeted antimetabolite strategy to exploit arginine deprivation with pegylated arginine deiminase (ADI-PEG20) as a therapeutic. ADI-PEG20 was synthetically lethal in ASS1-methylated bladder cells and its exposure was associated with a marked reduction in intracellular levels of thymidine, due to suppression of both uptake and de novo synthesis. We found that thymidine uptake correlated with thymidine kinase-1 protein levels and that thymidine levels were imageable with [(18)F]-fluoro-L-thymidine (FLT)-positron emission tomography (PET). In contrast, inhibition of de novo synthesis was linked to decreased expression of thymidylate synthase and dihydrofolate reductase. Notably, inhibition of de novo synthesis was associated with potentiation of ADI-PEG20 activity by the antifolate drug pemetrexed. Taken together, our findings argue that arginine deprivation combined with antifolates warrants clinical investigation in ASS1-negative urothelial

The impact of outpatient chemotherapy-related adverse events on the quality of life of breast cancer patients.

PubMed

Tachi, Tomoya; Teramachi, Hitomi; Tanaka, Kazuhide; Asano, Shoko; Osawa, Tomohiro; Kawashima, Azusa; Yasuda, Masahiro; Mizui, Takashi; Nakada, Takumi; Noguchi, Yoshihiro; Tsuchiya, Teruo; Goto, Chitoshi

2015-01-01

The objective of our study was to clarify the impact of adverse events associated with the initial course of outpatient chemotherapy on the quality of life of breast cancer patients. We conducted a survey to assess the quality of life in 48 breast cancer patients before and after receiving their first course of outpatient chemotherapy at Gifu Municipal Hospital. Patients completed the European Quality of Life 5 Dimensions and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs before and after 1 course of outpatient chemotherapy. European Quality of Life 5 Dimensions utility value and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs total score decreased significantly after chemotherapy (p<0.001 and p = 0.018, respectively). The mean scores for the activity, physical condition, and psychological condition subscales of the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs decreased significantly after chemotherapy (p = 0.003, p<0.001, and p = 0.032, respectively), whereas the social relationships score increased significantly (p<0.001). Furthermore, in the evaluation of quality of life according to individual adverse events, the decrease in quality of life after chemotherapy in terms of the European Quality of Life 5 Dimensions utility value and the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs total score was greater in anorexic patients than in non-anorexic patients (p = 0.009 and p<0.001, respectively). This suggests that anorexia greatly reduces quality of life. Our findings reveal that anticancer drug-related adverse events, particularly anorexia, reduce overall quality of life following the first course of outpatient chemotherapy in current breast cancer patients. These findings are extremely useful and important in understanding the impact of anticancer drug-related adverse events on quality of life.

Prognostic significance of peripheral monocyte count in patients with extranodal natural killer/T-cell lymphoma.

PubMed

Huang, Jia-Jia; Li, Ya-Jun; Xia, Yi; Wang, Yu; Wei, Wen-Xiao; Zhu, Ying-Jie; Lin, Tong-Yu; Huang, Hui-Qiang; Jiang, Wen-Qi; Li, Zhi-Ming

2013-05-03

Extranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL. Retrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis. The AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category. The baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL.

Prognostic significance of peripheral monocyte count in patients with extranodal natural killer/T-cell lymphoma

PubMed Central

2013-01-01

Background Extranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL. Methods Retrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis. Results The AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category. Conclusion The baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL. PMID:23638998

Prognostic impact of perineural invasion and lymphovascular invasion in advanced stage oral squamous cell carcinoma.

PubMed

Jardim, J F; Francisco, A L N; Gondak, R; Damascena, A; Kowalski, L P

2015-01-01

Perineural invasion (PNI) and lymphovascular invasion (LVI) have been associated with the risk of local recurrences and lymph node metastasis. The aim of this study was to evaluate the prognostic impact of PNI and LVI in patients with advanced stage squamous cell carcinoma of the tongue and floor of the mouth. One hundred and forty-two patients without previous treatment were selected. These patients underwent radical surgery with neck dissection and adjuvant treatment. Clinicopathological data were retrieved from the medical charts, including histopathology and surgery reports. Univariate analysis was performed to assess the impact of studied variables on survival. Overall survival was negatively influenced by six tumour-related factors: increasing T stage (P = 0.003), more than two clinically positive nodes (P = 0.002), extracapsular spread of lymph node metastasis (P < 0.001), tumour thickness (P = 0.04), PNI (P < 0.001), and LVI (P = 0.012). Disease-free survival was influenced by PNI (P = 0.04), extracapsular spread of lymph node metastasis (P = 0.008), and N stage (P = 0.006). Multivariate analysis showed PNI to be an independent predictor for overall survival (P = 0.01) and disease-free survival (P = 0.03). Thus the presence of PNI in oral carcinoma surgical specimens has a significant impact on survival outcomes in patients with advanced stage tumours submitted to radical surgery and adjuvant radiotherapy/radiochemotherapy. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Sex-specific impact of early-life adversity on chronic pain: a large population-based study in Japan.

PubMed

Yamada, Keiko; Matsudaira, Ko; Tanaka, Eizaburo; Oka, Hiroyuki; Katsuhira, Junji; Iso, Hiroyasu

2017-01-01

Responses to early-life adversity may differ by sex. We investigated the sex-specific impact of early-life adversity on chronic pain, chronic multisite pain, and somatizing tendency with chronic pain. We examined 4229 respondents aged 20-79 years who participated in the Pain Associated Cross-Sectional Epidemiological Survey in Japan. Outcomes were: 1) chronic pain prevalence, 2) multisite pain (≥3 sites) prevalence, and 3) multiple somatic symptoms (≥3 symptoms) among respondents with chronic pain related to the presence or absence of early-life adversity. Multivariable-adjusted odds ratios (ORs) were calculated with 95% confidence intervals using a logistic regression model including age, smoking status, exercise routine, sleep time, body mass index, household expenditure, and the full distribution of scores on the Mental Health Inventory-5. We further adjusted for pain intensity when we analyzed the data for respondents with chronic pain. The prevalence of chronic pain was higher among respondents reporting the presence of early-life adversity compared with those reporting its absence, with multivariable ORs of 1.62 (1.22-2.15, p <0.01) in men and 1.47 (1.13-1.90, p <0.01) in women. Among women with chronic pain, early-life adversity was associated with multisite pain and multiple somatic symptoms; multivariable ORs were 1.78 (1.22-2.60, p <0.01) for multisite pain and 1.89 (1.27-2.83, p <0.01) for ≥3 somatic symptoms. No associations were observed between early-life adversity and chronic multisite pain or multiple somatic symptoms among men with chronic pain. Early-life adversity may be linked to a higher prevalence of chronic pain among both sexes and to multisite pain and somatizing tendency among women with chronic pain.

Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients

PubMed Central

Martin, Stewart G.; Lebot, Marie N.; Sukkarn, Bhudsaban; Ball, Graham; Green, Andrew R.; Rakha, Emad A.; Ellis, Ian O.; Storr, Sarah J.

2018-01-01

G protein-coupled oestrogen receptor 1 (GPER), also called G protein-coupled receptor 30 (GPR30), is attracting considerable attention for its potential role in breast cancer development and progression. Activation by oestrogen (17β-oestradiol; E2) initiates short term, non-genomic, signalling events both in vitro and in vivo. Published literature on the prognostic value of GPER protein expression in breast cancer indicates that further assessment is warranted. We show, using immunohistochemistry on a large cohort of primary invasive breast cancer patients (n=1245), that low protein expression of GPER is not only significantly associated with clinicopathological and molecular features of aggressive behaviour but also significantly associated with adverse survival of breast cancer patients. Furthermore, assessment of GPER mRNA levels in the METABRIC cohort (n=1980) demonstrates that low GPER mRNA expression is significantly associated with adverse survival of breast cancer patients. Using artificial neural networks, genes associated with GPER mRNA expression were identified; these included notch-4 and jagged-1. These results support the prognostic value for determination of GPER expression in breast cancer. PMID:29899833

Male gender and renal dysfunction are predictors of adverse outcome in nonpostoperative ischemic colitis patients.

PubMed

Lee, Tsung-Chun; Wang, Hsiu-Po; Chiu, Han-Mo; Lien, Wan-Ching; Chen, Mei-Jyh; Yu, Linda C H; Sun, Chia-Tung; Lin, Jaw-Town; Wu, Ming-Shiang

2010-01-01

Ischemic colitis (IC) spans a broad spectrum from self-limiting illness to intestinal gangrene and mortality. Prognostic factors specifically for nonpostoperative IC were not fully characterized. We aim to focus on nonpostoperative IC in patients with renal dysfunction and try to identify prognostic factors for adverse outcomes. We conducted a retrospective analysis at a university-affiliated tertiary medical center in Taiwan. From January 2003 to August 2008, 25 men and 52 women (mean age: 66 y) had colonoscopic biopsy-proven IC without prior culprit surgery. We estimated glomerular filtration rate with simplified Modification of Diet in Renal Disease equation. Nine patients with glomerular filtration rate below 30 mL per minute per 1.73 m were classified as renal dysfunction group (including 7 dialysis patients). Adverse outcomes were defined as need for surgery and mortality. Predictors for adverse outcomes were captured by univariate and multivariate analysis. Research ethical committee approved the study protocol. Patients with renal dysfunction more often had: diabetes mellitus (56% vs. 16%, P=0.02), prolonged symptoms (6.8 d vs. 3.5 d, P=0.01), lower hemoglobin (11.1 g/dL vs. 13.4 g/dL, P=0.01), and more often right colonic involvement (56% vs. 19%, P=0.03). Renal dysfunction patients also had longer hospitalization days (median 15 d vs. 4 d, P=0.045). However, there was no statistical significance in the rate of either surgery or mortality between these 2 groups (P>0.05). Univariate analysis showed that renal dysfunction, sex, emergency department referral, presentation with abdominal pain were significant for adverse outcome (P<0.1). Multivariate analysis revealed that male sex conveyed 9.5-fold risk (P=0.01) and renal dysfunction conveyed 8.5-fold risk (P=0.03) for adverse outcomes. Nonpostoperative IC patients with concurrent renal dysfunction had distinct clinical profiles. Multivariate analysis showed that male patients had 9.5-fold and renal

Neuroblastoma in children: Update on clinicopathologic and genetic prognostic factors.

PubMed

Ahmed, Atif A; Zhang, Lei; Reddivalla, Naresh; Hetherington, Maxine

2017-04-01

Neuroblastoma is the most common extracranial solid tumor in childhood accounting for 8-10% of all childhood malignancies. The tumor is characterized by a spectrum of histopathologic features and a heterogeneous clinical phenotype. Modern multimodality therapy results in variable clinical response ranging from cure in localized tumors to limited response in aggressive metastatic disease. Accurate clinical staging and risk assessment based on clinical, surgical, biologic and pathologic criteria are of pivotal importance in assigning prognosis and planning effective treatment approaches. Numerous studies have analyzed the presence of several clinicopathologic and biologic factors in association with the patient's prognosis and outcome. Although patient's age, tumor stage, histopathologic classification, and MYCN amplification are the most commonly validated prognostic markers, several new gene mutations have been identified in sporadic and familial neuroblastoma cases that show association with an adverse outcome. Novel molecular studies have also added data on chromosomal segmental aberrations in MYCN nonamplified tumors. In this review, we provide an updated summary of the clinical, serologic and genetic prognostic indicators in neuroblastoma including classic factors that have consistently played a role in risk stratification of patients as well as newly discovered biomarkers that may show a potential significance in patients' management.

Prognostic impact of elevated serum uric acid levels on long-term outcomes in patients with chronic heart failure: A post-hoc analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) trial.

PubMed

Mantovani, Alessandro; Targher, Giovanni; Temporelli, Pier Luigi; Lucci, Donata; Gonzini, Lucio; Nicolosi, Gian Luigi; Marchioli, Roberto; Tognoni, Gianni; Latini, Roberto; Cosmi, Franco; Tavazzi, Luigi; Maggioni, Aldo Pietro

2018-06-01

The prognostic impact of hyperuricemia on long-term clinical outcomes in patients with chronic heart failure (HF) has been investigated in observational registries and clinical trials, but the results have been often inconclusive. We examined the prognostic impact of elevated serum uric acid levels on long-term clinical outcomes in the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) trial. CLINICALTRIALS. NCT00336336. We assessed the rates of all-cause death, cardiovascular death, cardiovascular hospitalization and the composite of all-cause death or cardiovascular hospitalization over a median follow-up of 3.9 years among 6683 ambulatory patients with chronic HF. Patients in the 3rd serum uric acid tertile (>7.2 mg/dl) had a nearly 1.8-fold increased risk of both all-cause death and cardiovascular death, and a nearly 1.5-fold increased risk of cardiovascular hospitalization and of the composite endpoint compared to those in the 1st uric acid tertile (<5.7 mg/dl). Beyond serum uric acid ≥ 7 mg/dl the risk of outcomes increased sharply and linearly. The significant association between elevated serum uric acid levels and adverse outcomes persisted after adjustment for multiple established cardiovascular risk factors, HF etiology, left ventricular ejection fraction, medication use and other potential confounders, with an adjusted hazard ratio of 1.37 (95% CI 1.22-1.55) for all-cause death, 1.48 (1.29-1.69) for cardiovascular death, 1.19 (1.09-1.30) for cardiovascular hospitalization and 1.21 (1.11-1.31) for the composite endpoint, respectively. Elevated serum uric acid levels are independently associated with poor long-term survival and increased risk of cardiovascular hospitalization in patients with chronic HF. Copyright © 2018 Elsevier Inc. All rights reserved.

A Distributed Approach to System-Level Prognostics

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, Indranil

2012-01-01

Prognostics, which deals with predicting remaining useful life of components, subsystems, and systems, is a key technology for systems health management that leads to improved safety and reliability with reduced costs. The prognostics problem is often approached from a component-centric view. However, in most cases, it is not specifically component lifetimes that are important, but, rather, the lifetimes of the systems in which these components reside. The system-level prognostics problem can be quite difficult due to the increased scale and scope of the prognostics problem and the relative Jack of scalability and efficiency of typical prognostics approaches. In order to address these is ues, we develop a distributed solution to the system-level prognostics problem, based on the concept of structural model decomposition. The system model is decomposed into independent submodels. Independent local prognostics subproblems are then formed based on these local submodels, resul ting in a scalable, efficient, and flexible distributed approach to the system-level prognostics problem. We provide a formulation of the system-level prognostics problem and demonstrate the approach on a four-wheeled rover simulation testbed. The results show that the system-level prognostics problem can be accurately and efficiently solved in a distributed fashion.

Prognostic impact of CXCL16 and CXCR6 in non-small cell lung cancer: combined high CXCL16 expression in tumor stroma and cancer cells yields improved survival.

PubMed

Hald, Sigurd M; Kiselev, Yury; Al-Saad, Samer; Richardsen, Elin; Johannessen, Charles; Eilertsen, Marte; Kilvaer, Thomas K; Al-Shibli, Khalid; Andersen, Sigve; Busund, Lill-Tove; Bremnes, Roy M; Donnem, Tom

2015-05-29

The chemokine CXCL16 and its receptor CXCR6 are expressed by a variety of immune cells and have been shown to influence angiogenesis. The expression of CXCR6 and CXCL16 has been examined in numerous human cancers; however no studies have yet investigated their influence on prognosis in non-small cell lung cancer (NSCLC). We aimed to explore their prognostic significance in NSCLC, in addition to examining associations with previously investigated markers. Resected tumor tissue from 335 consecutive unselected stage I-IIIA NSCLC patients (1990-2005) were collected. Immunohistochemistry was used to evaluate the expression of CXCR6 and CXCL16 on tissue microarrays. In vitro, NSCLC cells (NCI-H460, A549 cells) were transfected with CXCL16 siRNA to examine effects on proliferation. In univariate analysis, ↑ stromal cell CXCL16 expression was a significant positive prognostic factor (P = 0.016). CXCR6 was expressed in cancer cells, but did not show any prognostic impact. In the multivariate analysis, combined ↑cancer, and ↑stromal cell CXCL16 expression was an independent positive prognostic factor when compared to ↓stromal and ↓cancer cell expression (HR: 0.42; 95 % CI: 0.20-0.88; P = 0.022). Knockdown of CXCL16 by siRNA resulted in accelerated proliferation of NSCLC cell lines. We have shown that combined ↑cancer and ↑stromal cell CXCL16 expression is an independent positive prognostic factor in NSCLC. Further studies are warranted to elucidate the biological mechanism underlying this finding.

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

PubMed Central

Lee, Yi-Ying; Wei, Yu-Ching; Tian, Yu-Feng; Sun, Ding-Ping; Sheu, Ming-Jen; Yang, Ching-Chieh; Lin, Li-Ching; Lin, Chen-Yi; Hsing, Chung-Hsi; Li, Wan-Shan; Li, Chien-Feng; Hsieh, Pei-Ling; Lin, Ching-Yih

2017-01-01

Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT. Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS). Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p<0.001) and nodal status (N1, N2; p<0.001), vascular invasion (p=0.003) and inferior tumor regression grade (p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS (p<0.0001), MeFS (p=0.0002) and LRFS (p=0.0001). Furthermore, it remained an independent prognosticator of worse DSS (p=0.002, hazard ratio=3.344), MeFS (p=0.021, hazard ratio=3.015) and LRFS (p=0.037, hazard ratio=3.037) in the multivariate comparison. Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy.

PubMed

Lee, Yi-Ying; Wei, Yu-Ching; Tian, Yu-Feng; Sun, Ding-Ping; Sheu, Ming-Jen; Yang, Ching-Chieh; Lin, Li-Ching; Lin, Chen-Yi; Hsing, Chung-Hsi; Li, Wan-Shan; Li, Chien-Feng; Hsieh, Pei-Ling; Lin, Ching-Yih

2017-01-01

Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT. Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS). Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p <0.001) and nodal status (N1, N2; p <0.001), vascular invasion ( p =0.003) and inferior tumor regression grade ( p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS ( p <0.0001), MeFS ( p =0.0002) and LRFS ( p =0.0001). Furthermore, it remained an independent prognosticator of worse DSS ( p =0.002, hazard ratio=3.344), MeFS ( p =0.021, hazard ratio=3.015) and LRFS ( p =0.037, hazard ratio=3.037) in the multivariate comparison. Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and

Neoadjuvant oral vs. infusional chemoradiotherapy on locally advanced rectal cancer: Prognostic factors.

PubMed

Conde, Sofia; Borrego, Margarida; Teixeira, Tânia; Teixeira, Rubina; Sá, Anabela; Soares, Paula

2012-01-01

To evaluate the prognostic factors and impact on survival of neoadjuvant oral and infusional chemoradiotherapy in patients with locally advanced rectal cancer. There is still no definitive consensus about the prognostic factors and the impact of neoadjuvant chemoradiotherapy on survival. Some studies have pointed to an improvement in overall survival (OS) and progression-free survival (PFS) in patients with tumor downstaging (TD) and nodal downstaging (ND). A set of 159 patients with LARC were treated preoperatively. Group A - 112 patients underwent concomitant oral chemoradiotherapy: capecitabine or UFT + folinic acid. Group B - 47 patients submitted to concomitant chemoradiation with 5-FU in continuous infusion. 63.6% of patients were submitted to adjuvant chemotherapy. pathologic complete response (pCR) - 18.7%; TD - 55.1%; ND - 76%; loco-regional response - 74.8%. Group B: pCR - 11.4%; TD - 50%; ND - 55.8%; LRR - 54.5%. The loco-regional control was 95.6%. There was no difference in survival between both groups. Those with loco-regional response had better PFS. Tumor and nodal downstaging, loco-regional response and a normal CEA level turned out to be important prognostic factors in locally advanced rectal cancer. Nodal downstaging and loco-regional response were higher in Group A. Those with tumor downstaging and loco-regional response from Group A had better OS. Adjuvant chemotherapy had no impact on survival except in those patients with loco-regional response who achieved a higher PFS.

Adverse reactions and other factors that impact subsequent blood donation visits.

PubMed

Custer, Brian; Rios, Jorge A; Schlumpf, Karen; Kakaiya, Ram M; Gottschall, Jerome L; Wright, David J

2012-01-01

The importance of adverse reactions in terms of donor safety recently has received significant attention, but their role in subsequent donation behavior has not been thoroughly investigated. Six REDS-II blood centers provided data for this analysis. Summary minor and major adverse reaction categories were created. The influence of adverse reactions on donation was examined in two ways: Kaplan-Meier curves were generated to determine the cumulative pattern of first return, and adjusted odds ratios (AORs) for demographic and other factors positively and negatively associated with return were estimated using multivariable logistic regression. Donors who had major reactions had longer times to return than donors with minor or no reactions. The AOR of returning for donors with major reactions was 0.32 (95% confidence interval [CI], 0.28-0.37) and with minor reactions 0.59 (95% CI, 0.56-0.62) when compared to donors who did not have reactions. Conversely, the most important factors positively associated with return were the number of donations in the previous year and increasing age. Subsequent return, whether a major, minor, or no reaction occurred, varied by blood center. Factors that are associated with the risk of having adverse reactions were not substantial influences on the return after adverse reactions. Having an adverse reaction leads to significantly lower odds of subsequent donation irrespective of previous donation history. Factors that have been associated with a greater risk of adverse reactions were not important positive or negative predictors of return after a reaction. © 2011 American Association of Blood Banks.

Generic Software Architecture for Prognostics (GSAP) User Guide

NASA Technical Reports Server (NTRS)

Teubert, Christopher Allen; Daigle, Matthew John; Watkins, Jason; Sankararaman, Shankar; Goebel, Kai

2016-01-01

The Generic Software Architecture for Prognostics (GSAP) is a framework for applying prognostics. It makes applying prognostics easier by implementing many of the common elements across prognostic applications. The standard interface enables reuse of prognostic algorithms and models across systems using the GSAP framework.

The divergent impact of catechol-O-methyltransferase (COMT) Val158Met genetic polymorphisms on executive function in adolescents with discrete patterns of childhood adversity.

PubMed

Zhang, Huihui; Li, Jie; Yang, Bei; Ji, Tao; Long, Zhouting; Xing, Qiquan; Shao, Di; Bai, Huayu; Sun, Jiwei; Cao, Fenglin

2018-02-01

Catechol-O-methyltransferase (COMT) Val 158 Met functional polymorphisms play a crucial role in the development of executive function (EF), but their effect may be moderated by environmental factors such as childhood adversity. The present study aimed at testing the divergent impact of the COMT Val 158 Met genotype on EF in non-clinical adolescents with discrete patterns of childhood adversity. A total of 341 participants completed the Childhood Trauma Questionnaire, the self-reported version of the Behavior Rating Inventory of Executive Function, and self-administered questionnaires on familial function. The participants' COMT Val 158 Met genotype was determined. Associations among the variables were explored using latent class analysis and general linear models. We found that Val/Val homozygotes showed significantly worse performance on behavioral shift, relative to Met allele carriers (F=5.921, p=0.015, Partial η 2 =0.018). Moreover, three typical patterns of childhood adversity, namely, low childhood adversity (23.5%), childhood neglect (59.8%), and high childhood adversity (16.7%), were found. Both childhood neglect and high childhood adversity had a negative impact on each aspect of EF and on global EF performance. Importantly, these results provided evidence for significant interaction effects, as adolescents with the Val/Val genotype showed inferior behavioral shift performance than Met carriers (F=6.647, p=0.010, Partial η 2 =0.020) in the presence of high childhood adversity. Furthermore, there were no differences between the genotypes for childhood neglect and low childhood adversity. Overall, this is the first study to show that an interaction between the COMT genotype and childhood adversity affects EF in non-clinical adolescents. These results suggest that the COMT genotype may operate as a susceptibility gene vulnerable to an adverse environment. Copyright © 2017 Elsevier Inc. All rights reserved.

Distilling the Verification Process for Prognostics Algorithms

NASA Technical Reports Server (NTRS)

Roychoudhury, Indranil; Saxena, Abhinav; Celaya, Jose R.; Goebel, Kai

2013-01-01

The goal of prognostics and health management (PHM) systems is to ensure system safety, and reduce downtime and maintenance costs. It is important that a PHM system is verified and validated before it can be successfully deployed. Prognostics algorithms are integral parts of PHM systems. This paper investigates a systematic process of verification of such prognostics algorithms. To this end, first, this paper distinguishes between technology maturation and product development. Then, the paper describes the verification process for a prognostics algorithm as it moves up to higher maturity levels. This process is shown to be an iterative process where verification activities are interleaved with validation activities at each maturation level. In this work, we adopt the concept of technology readiness levels (TRLs) to represent the different maturity levels of a prognostics algorithm. It is shown that at each TRL, the verification of a prognostics algorithm depends on verifying the different components of the algorithm according to the requirements laid out by the PHM system that adopts this prognostics algorithm. Finally, using simplified examples, the systematic process for verifying a prognostics algorithm is demonstrated as the prognostics algorithm moves up TRLs.

Impact of Early Life Adversity on Reward Processing in Young Adults: EEG-fMRI Results from a Prospective Study over 25 Years

PubMed Central

Boecker, Regina; Holz, Nathalie E.; Buchmann, Arlette F.; Blomeyer, Dorothea; Plichta, Michael M.; Wolf, Isabella; Baumeister, Sarah; Meyer-Lindenberg, Andreas; Banaschewski, Tobias

2014-01-01

Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway. PMID:25118701

Evaluating biomarkers for prognostic enrichment of clinical trials.

PubMed

Kerr, Kathleen F; Roth, Jeremy; Zhu, Kehao; Thiessen-Philbrook, Heather; Meisner, Allison; Wilson, Francis Perry; Coca, Steven; Parikh, Chirag R

2017-12-01

A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

Pre-Treatment Anemia Is a Poor Prognostic Factor in Soft Tissue Sarcoma Patients

PubMed Central

Szkandera, Joanna; Gerger, Armin; Liegl-Atzwanger, Bernadette; Stotz, Michael; Samonigg, Hellmut; Ploner, Ferdinand; Stojakovic, Tatjana; Leithner, Andreas; Pichler, Martin

2014-01-01

Background Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery. Methods Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb<13 g/dl in males and Hb<12 g/dl in females according to the current WHO guidelines. The impact of pre-operative Hb levels on cancer-specific survival (CSS) and overall survival (OS) was assessed using Kaplan-Meier curves. Additionally, Hb levels were compared for the prognostic influence on CSS and OS applying univariate and multivariate Cox proportional models. Results Hb level was associated with established prognostic factors, including age, tumor grade, size and depth (p<0.05). Kaplan-Meier curves showed that low Hb levels were significantly associated with decreased CSS and OS in STS patients (p<0.001 for both endpoints, log-rank test). In multivariate analysis, we found an independent association between low Hb levels and poor CSS and OS (HR = 0.46, Cl 95% = 0.25–0.85, p = 0.012; HR = 0.34, Cl 95% = 0.23–0.51, p<0.001). Conclusion The present data underline a negative prognostic impact of low pre-operative Hb levels on clinical outcome in STS patients. Thus, Hb levels may provide an additional and cost-effective tool to discriminate between STS patients that are at high risk of mortality. PMID:25207808

Adversity and psychosis: a 10-year prospective study investigating synergism between early and recent adversity in psychosis.

PubMed

Lataster, J; Myin-Germeys, I; Lieb, R; Wittchen, H-U; van Os, J

2012-05-01

Recent studies have suggested that early adverse events, such as childhood trauma, may promote enduring liability for psychosis whereas more recent adverse events may act as precipitants. Examination of these environmental dynamics, however, requires prospective studies in large samples. This study examines whether the association between recent adverse events and psychosis is moderated by exposure to early adversity. A random regional representative population sample of 3021 adolescents and young adults in Munich, Germany, was assessed three times over a period of up to 10 years, collecting information on sociodemographic factors, environmental exposures, and measures of psychopathology and associated clinical relevance. Evidence of statistical non-additivity between early adversity (two levels) and more recent adversity (four levels) was assessed in models of psychotic symptoms. Analyses were a priori corrected for age, gender, cannabis use, and urbanicity. Early and recent adversity were associated with each other (RR = 1.32, 95% CI 1.06-1.66; P = 0.014) and displayed statistical non-additivity at the highest level of exposure to recent adversity (χ(2) = 4.59; P = 0.032). The findings suggest that early adversity may impact on later expression of psychosis either by increasing exposure to later adversity and/or by rendering individuals more sensitive to later adversity if it is severe. © 2011 John Wiley & Sons A/S.

Prognostic Importance of Small Prostate Size in Men Receiving Definitive Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taira, Al V.; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org; Galbreath, Robert W.

Purpose: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. Methods and Materials: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size ({<=}20 cm{sup 3}) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. Results: Median prostate sizemore » for the entire cohort was 32.7 cm{sup 3}. For the 167 men with small prostates, median prostate size was 17.4 cm{sup 3}. There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. Conclusion: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.« less

Unpacking the impact of adverse childhood experiences on adult mental health.

PubMed

Merrick, Melissa T; Ports, Katie A; Ford, Derek C; Afifi, Tracie O; Gershoff, Elizabeth T; Grogan-Kaylor, Andrew

2017-07-01

Exposure to childhood adversity has an impact on adult mental health, increasing the risk for depression and suicide. Associations between Adverse Childhood Experiences (ACEs) and several adult mental and behavioral health outcomes are well documented in the literature, establishing the need for prevention. The current study analyzes the relationship between an expanded ACE score that includes being spanked as a child and adult mental health outcomes by examining each ACE separately to determine the contribution of each ACE. Data were drawn from Wave II of the CDC-Kaiser ACE Study, consisting of 7465 adult members of Kaiser Permanente in southern California. Dichotomous variables corresponding to each of the 11 ACE categories were created, with ACE score ranging from 0 to 11 corresponding to the total number of ACEs experienced. Multiple logistic regression modeling was used to examine the relationship between ACEs and adult mental health outcomes adjusting for sociodemographic covariates. Results indicated a graded dose-response relationship between the expanded ACE score and the likelihood of moderate to heavy drinking, drug use, depressed affect, and suicide attempts in adulthood. In the adjusted models, being spanked as a child was significantly associated with all self-reported mental health outcomes. Over 80% of the sample reported exposure to at least one ACE, signifying the potential to capture experiences not previously considered by traditional ACE indices. The findings highlight the importance of examining both cumulative ACE scores and individual ACEs on adult health outcomes to better understand key risk and protective factors for future prevention efforts. Copyright © 2017. Published by Elsevier Ltd.

Scoring Method of a Situational Judgment Test: Influence on Internal Consistency Reliability, Adverse Impact and Correlation with Personality?

ERIC Educational Resources Information Center

De Leng, W. E.; Stegers-Jager, K. M.; Husbands, A.; Dowell, J. S.; Born, M. Ph.; Themmen, A. P.

2017-01-01

Situational Judgment Tests (SJTs) are increasingly used for medical school selection. Scoring an SJT is more complicated than scoring a knowledge test, because there are no objectively correct answers. The scoring method of an SJT may influence the construct and concurrent validity and the adverse impact with respect to non-traditional students.…

Estimating the Potential Impact of Tobacco Control Policies on Adverse Maternal and Child Health Outcomes in the United States Using the SimSmoke Tobacco Control Policy Simulation Model.

PubMed

Levy, David; Mohlman, Mary Katherine; Zhang, Yian

2016-05-01

Numerous studies document the causal relationship between prenatal smoking and adverse maternal and child health (MCH) outcomes. Studies also reveal the impact that tobacco control policies have on prenatal smoking. The purpose of this study is to estimate the effect of tobacco control policies on prenatal smoking prevalence and adverse MCH outcomes. The US SimSmoke simulation model was extended to consider adverse MCH outcomes. The model estimates prenatal smoking prevalence and, applying standard attribution methods, uses estimates of MCH prevalence and relative smoking risks to estimate smoking-attributable MCH outcomes over time. The model then estimates the effect of tobacco control policies on adverse birth outcomes averted. Different tobacco control policies have varying impacts on the number of smoking-attributable adverse MCH birth outcomes. Higher cigarette taxes and comprehensive marketing bans individually have the biggest impact with a 5% to 10% reduction across all outcomes for the period from 2015 to 2065. The policies with the lowest impact (2%-3% decrease) during this period are cessation treatment, health warnings, and complete smoke-free laws. Combinations of all policies with each tax level lead to 23% to 28% decreases across all outcomes. Our findings demonstrate the substantial impact of strong tobacco control policies for preventing adverse MCH outcomes, including long-term health implications for children exposed to low birth weight and preterm birth. These benefits are often overlooked in discussions of tobacco control. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Diagnostic and prognostic value of N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with chronic aortic regurgitation.

PubMed

Weber, Michael; Hausen, Michael; Arnold, Roman; Moellmann, Helge; Nef, Holger; Elsaesser, Albrecht; Mitrovic, Vesselin; Hamm, Christian

2008-07-21

BNP and its N-terminal fragment NT-proBNP have proven to be of diagnostic and prognostic value in patients with valvular aortic stenosis. Data regarding those biomarkers in patients with chronic aortic regurgitation (AR) are sparse. Thus it was the aim of the present study to evaluate the diagnostic and the long term prognostic value of NT-proBNP in patients presenting with AR. This study included 60 patients with isolated AR of varying severity (AR I mild, AR II moderate and AR III severe) and preserved left ventricular function. Patients were followed over a median period of 824 (770-921) days. NT-proBNP at baseline was related to disease severity and to functional status (161 (70-456) pg/ml in AR I, 226 (100-666) pg/ml in AR II and 1268 (522-5446) pg/ml in AR III (p=0.003)). Patients (n=6) experiencing an adverse event had higher NT-proBNP values at baseline as event free survivors (1271 (613-2992) pg/ml vs. 215 (92-534) pg/ml; p=0.034). The AUC of the ROC curve for NT-proBNP as a predictor for an adverse event was 0.76 (p<0.036) with an optimised cut-off value of 602 pg/ml. Consequently, in Kaplan-Meier analysis NT-proBNP values dichotomised at this cut-off were able to discriminate patients with an adverse outcome in the entire study group (Log rank 9.98, p=0.0016) and even better in the conservative group (Log rank 26.92, p<0.001). NT-proBNP is linked to disease severity in patients with chronic aortic regurgitation reflecting hemodynamic stress due to volume overload. It provides prognostic information for the clinical outcome and thus might be a useful biomarker for risk stratification.

Improving the Prognostic Ability through Better Use of Standard Clinical Data - The Nottingham Prognostic Index as an Example

PubMed Central

Winzer, Klaus-Jürgen; Buchholz, Anika; Schumacher, Martin; Sauerbrei, Willi

2016-01-01

Background Prognostic factors and prognostic models play a key role in medical research and patient management. The Nottingham Prognostic Index (NPI) is a well-established prognostic classification scheme for patients with breast cancer. In a very simple way, it combines the information from tumor size, lymph node stage and tumor grade. For the resulting index cutpoints are proposed to classify it into three to six groups with different prognosis. As not all prognostic information from the three and other standard factors is used, we will consider improvement of the prognostic ability using suitable analysis approaches. Methods and Findings Reanalyzing overall survival data of 1560 patients from a clinical database by using multivariable fractional polynomials and further modern statistical methods we illustrate suitable multivariable modelling and methods to derive and assess the prognostic ability of an index. Using a REMARK type profile we summarize relevant steps of the analysis. Adding the information from hormonal receptor status and using the full information from the three NPI components, specifically concerning the number of positive lymph nodes, an extended NPI with improved prognostic ability is derived. Conclusions The prognostic ability of even one of the best established prognostic index in medicine can be improved by using suitable statistical methodology to extract the full information from standard clinical data. This extended version of the NPI can serve as a benchmark to assess the added value of new information, ranging from a new single clinical marker to a derived index from omics data. An established benchmark would also help to harmonize the statistical analyses of such studies and protect against the propagation of many false promises concerning the prognostic value of new measurements. Statistical methods used are generally available and can be used for similar analyses in other diseases. PMID:26938061

Prognostic impact of blood biomarkers TS and DPD in neoadjuvant-treated esophageal cancer patients.

PubMed

Grimminger, Peter P; Maus, Martin K H; Bergenthal, Juliane; Wandhöfer, Christoph; Fetzner, Ullrich K; Herbold, Till; Bollschweiler, Elfriede; Hölscher, Arnulf H; Brabender, Jan

2015-03-01

The prognostic value of TS (thymidylate synthase) and DPD (dihydropyrimidine dehydrogenase) RNA expression in the blood of patients with esophageal cancer is not known. The aim of the present study was to evaluate the significance of these molecular alterations in the blood as a prognostic marker for patients with neoadjuvant-treated esophageal cancer. A total of 29 patients with locally advanced esophageal cancer (cT3-T4, Nx, M0) were enrolled in this prospective study. All patients received neoadjuvant chemoradiation followed by a transthoracic resection (curative transthoracic en bloc esophagectomy, RO). Peripheral blood samples were drawn before initiation of therapy. The analysis was performed using quantitative real-time-polymerase chain reaction (RT-PCR). The histomorphological regressions grading after neoadjuvant therapy was defined as follows: major response (MaR)=less than 10% vital tumor tissue, minor response (MiR)=more than 10% vital tumor tissue. Nineteen out of 29 patients (65.5%) had a MiR and 10 (34.5%) had a MaR. The median survival of patients was 2.08 years (range=0.15-4.53). Among the tested genes, the RNA expression of TS was significantly associated with prognosis of patients. Patients with TS expression above 0.78 had a median survival of 1.1 years (range=0.21-3.96) compared to 2.6 years (range=0.15 to 4.53) in patients with TS expression lower than 0.78 (p=0.031, log rank test). There was no association between clinical variables (e.g., tumor stage, gender, age, etc.) and the RNA expression of TS in the serum. The RNA expression of TS in the blood is a potential prognostic marker in patients with neoadjuvant-treated esophageal cancer. The significance of these molecular alterations as non-invasive prognostic marker for esophageal cancer should be evaluated in prospective studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Serum prognostic biomarkers in head and neck cancer patients.

PubMed

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J; Tainsky, Michael A

2014-08-01

A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Prospective cohort study. A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient's serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Poor overall survival was associated with African Americans (hazard ratio [HR] for death = 2.61; 95% confidence interval [CI]: 1.58-4.33; P = .000), advanced stage (HR = 2.79; 95% CI: 1.40-5.57; P = .004), and recurrent disease (HR = 6.66; 95% CI: 2.54-17.44; P = .000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Serum Prognostic Biomarkers in Head and Neck Cancer Patients

PubMed Central

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S.; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H.; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J.; Tainsky, Michael A.

2014-01-01

Objectives/Hypothesis A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Study Design Prospective cohort study. Methods A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient’s serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Results Poor overall survival was associated with African Americans (hazard ratio [HR] for death =2.61; 95% confidence interval [CI]: 1.58–4.33; P =.000), advanced stage (HR =2.79; 95% CI: 1.40–5.57; P =.004), and recurrent disease (HR =6.66; 95% CI: 2.54–17.44; P =.000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. Conclusions The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. PMID:24347532

Analysis of the prognostic value of BMI and the difference in its impact according to age and sex in DLBCL patients.

PubMed

Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Tamura, Miho; Sawada, Takeshi; Omuro, Yasushi; Hishima, Tsunekazu; Maeda, Yoshiharu

2018-02-01

Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B-cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B-cell lymphoma patients treated with R-CHOP or R-CHOP-like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (<18.5 kg/m 2 ), 58 (14.3%); normal weight (≥18.5 to <25 kg/m 2 ), 262 (64.5%); overweight (≥25 to <30 kg/m 2 ), 75 (18.5%); and obese (≥30.0 kg/m 2 ), 11 (2.7%). While the prognosis of overweight patients was good, being similar to that of normal weight, underweight, and obese patients had a worse prognosis (5-y overall survival [OS] was 57.9%, 74.3%, 73.4%, and 40.9% for underweight, normal weight, overweight, and obese patients, respectively; P = .004). In multivariate analysis, underweight and obesity were independent prognostic factors for OS compared with normal weight (hazard ratios 2.90 and 5.17, respectively). In elderly female patients (≥70 y), patients with a low BMI (<25 kg/m 2 ) had significantly inferior OS than those with a high BMI (≥25 kg/m 2 ) (5-y OS, 61.5% vs 85.7%; P = .039). In contrast, in young female patients (<70 years), patients with a low BMI had significantly better OS than those with a high BMI (5-y OS, 88.6% vs 46.4%; P < .001). In male patients, there were no differences in the effect of BMI on OS between young and elderly patients. In this study, we demonstrated that being underweight and obese were independent prognostic factors compared with being normal weight. In female patients, BMI had a different impact on the prognosis of young and elderly patients, whereas in male patients, there was no difference in the effect of BMI on prognosis according to age. Copyright © 2017 John Wiley & Sons, Ltd.

Glasgow Prognostic Score as a Prognostic Clinical Marker in T4 Esophageal Squamous Cell Carcinoma.

PubMed

Ohira, Masaichi; Kubo, Naoshi; Masuda, Go; Yamashita, Yoshito; Sakurai, Katsunobu; Toyokawa, Takahiro; Tanaka, Hiroaki; Muguruma, Kazuya; Hirakawa, Kosei

2015-09-01

Patients with clinical T4 esophageal squamous cell carcinoma (ESCC) have an unfavorable prognosis, mainly indicated by the response to chemoradiotherapy (CRT), crucial to estimating long-term survival. Other prognostic measures include systemic inflammatory or immunonutritional indices such as the Glasgow Prognostic Score (GPS) and Prognostic Nutritional Index (PNI) that have not been sufficiently documented. This study retrospectively evaluated 91 patients with T4 ESCC treated at our Hospital between 2000 and 2013. All patients initially received CRT, including 5-fluorouracil (5FU) and cisplatin or nedaplatin with concurrent 2-Gy/fraction radiation (total dose, 40-60 Gy). Curative tumor resection was undertaken in suitable patients on completing CRT. Patients were classified as GPS0, GPS1, or GPS2 based on C-reactive protein (CRP) ≤ 10 mg/l and albumin ≥ 35 g/l, CRP >10 mg/l or albumin <35 g/l, or CRP >10 mg/l and albumin <35 g/l, respectively. PNI was calculated as 10-times the serum albumin (g/dl)+0.005 × total lymphocyte count (/mm(3)). The impact of the pre-treatment GPS and PNI on the prognosis of patients with T4 ESCC was investigated in univariate and multivariate analyses. Sixty (67%) patients responded to CRT (9 complete responses and 51 partial responses). Forty-one (45%) patients also underwent surgical resection of the residual tumor. The overall 5-year survival rate and median survival time were 27.0% and 11.8 months, respectively. In the cohort of CRT-plus-surgical resection, the 5-year survival rate was significantly higher than in the groups treated with CRT-alone (51.1% vs. 6.5%; p < 0.01). On multivariate analysis, good response to CRT [hazard ratio (HR) =0.449, p<0.01], GPS1/2 (HR=2.151, p=0.015), and surgical resection (HR=0.282, p<0.01) were significant prognostic factors, whereas PNI was not. The GPS is a useful, simple survival marker for patients with T4 ESCC undergoing multimodal therapy. Copyright© 2015 International Institute of

Prognostic factors in prostate cancer patients treated by radical external beam radiotherapy.

PubMed

Garibaldi, Elisabetta; Gabriele, Domenico; Maggio, Angelo; Delmastro, Elena; Garibaldi, Monica; Russo, Filippo; Bresciani, Sara; Stasi, Michele; Gabriele, Pietro

2017-09-01

The aim of this paper was to analyze, retrospectively, in prostate cancer patients treated in our Centre with external beam radiotherapy, the prognostic factors and their impact on the outcome in terms of cancer-specific survival (CSS), biochemical disease-free survival (BDFS) and clinical disease-free survival (CDFS). From October 1999 and March 2012, 1080 patients were treated with radiotherapy at our Institution: 87% of them were classified as ≤cT2, 83% had a Gleason Score (GS) ≤7, their mean of iPSA was 18 ng/mL, and the rate of clinical positive nodes was 1%. The mean follow-up was 81 months. The statistically significant prognostic factors for all groups of patients at both, univariate and multivariate analysis, were the GS and the iPSA. In intermediate- and high- or very-high-risk patients at multivariate analysis other prognostic factors for CSS were positive nodes on computed tomography (CT) scan and rectal preparation during the treatment; for BDFS, the prognostic factors were patient risk classification, positive lymph nodes on CT scan and rectal/bladder preparation; for CDFS, the prognostic factors were the number of positive core on biopsy (P=0.003), positive lymph nodes on CT scan, and radiotherapy (RT) dose. In high/very-high risk patient group at multivariate analysis other prognostic factors for CSS were clinical/radiological stage and RT dose, for BDFS they were adjuvant hormone therapy, clinical/radiological stage, and RT dose >77.7 Gy, and for CDFS they were clinical/radiological stage and RT dose >77.7 Gy. The results of this study confirm the prognostic factors described in the recent literature, with the addition of rectal/bladder preparation, generally known for its effect on toxicity but not yet on outcome.

Ongoing adverse mental health impact of the earthquake sequence in Christchurch, New Zealand.

PubMed

Spittlehouse, Janet K; Joyce, Peter R; Vierck, Esther; Schluter, Philip J; Pearson, John F

2014-08-01

In September 2010 Christchurch, New Zealand, was struck by a 7.1 magnitude earthquake, followed by a prolonged sequence of significant aftershocks including a fatal aftershock in February 2011. Christchurch City has experienced widespread damage, ongoing disruption and building demolitions resulting in many difficulties for the residents of the Christchurch area. We explore what impact the earthquakes have had on the mental and physical health of a random sample of 50-year-olds who live in the Christchurch area. The 295 participants were selected from the electoral rolls for participation in the CHALICE study, a longitudinal study of ageing. Self-reported health status was assessed using the standardised Short Form 36 version 2 health survey (SF-36v2), a 36-item questionnaire, and results from the eight subscales compared to a national health survey. Mood disorders were assessed and the results were compared to other local and national studies. Since the onset of the earthquakes and throughout the study period, participating middle-aged Christchurch residents have mean SF-36v2 scores significantly lower than population norms in the mental health, vitality, social functioning and role-emotional subscales (Cohen's d ranged from -0.270 to -0.357, all p < 0.001), while there was no evidence of reduced physical health. Rates of current major depressive disorder were 7.5% in the earthquake survivors compared to 5.1% and 3.7% in other historical, local and national surveys. Similarly, bipolar disorder prevalence was 2.8% in the earthquake survivors compared to 2.2% and 1.4% in other studies. Eighteen months after the first earthquake the significant adverse impact on mental health clearly continues. The ongoing provision of additional mental health services and consideration of these adverse mental health effects in relation to other social policies remains necessary and fundamental. © The Royal Australian and New Zealand College of Psychiatrists 2014.

Childhood Adversity and Pain Sensitization.

PubMed

You, Dokyoung Sophia; Meagher, Mary W

Childhood adversity is a vulnerability factor for chronic pain. However, the underlying pain mechanisms influenced by childhood adversity remain unknown. The aim of the current study was to evaluate the impact of childhood adversity on dynamic pain sensitivity in young adults. After screening for childhood adverse events and health status, healthy individuals reporting low (below median; n = 75) or high levels of adversity (the top 5%; n = 51) were invited for pain testing. Both groups underwent heat pain threshold and temporal summation of second pain (TSSP) testing after reporting depressive symptoms. TSSP refers to a progressive increase in pain intensity with repetition of identical noxious stimuli and is attributed to central sensitization. Changes in pain ratings over time (slope) were computed for TSSP sensitization and decay of subsequent aftersensations. The high-adversity group showed greater TSSP sensitization (meanslope, 0.75; SDpositive slope, 1.78), and a trend toward a slower decay (meanslope, -11.9; SD, 3.4), whereas the low-adversity group showed minimal sensitization (meanslope, 0.07; SDnear-zero slope, 1.77), F(1,123) = 5.84, p = .017 and faster decay (meanslope, -13.1; SD, 3.4), F(1,123) = 3.79, p = .054. This group difference remained significant even after adjusting for adult depressive symptoms (p = .033). No group difference was found in heat pain threshold (p = .85). Lastly, the high-adversity group showed blunted cardiac and skin conductance responses. These findings suggest that enhancement of central sensitization may provide a mechanism underlying the pain hypersensitivity and chronicity linked to childhood adversity.

The Glasgow Prognostic Score as a significant predictor of diffuse large B cell lymphoma treated with R-CHOP in China.

PubMed

Li, Xiaoyang; Zhang, Yunxiang; Zhao, Weili; Liu, Zhao; Shen, Yang; Li, Junmin; Shen, Zhixiang

2015-01-01

The Glasgow Prognostic Score (GPS) incorporates C-reactive protein and albumin as clinically useful markers of tumor behavior and shows significant prognostic value in several types of solid tumors. The accuracy of the GPS in predicting outcomes in diffuse large B cell lymphoma (DLBCL) remains unknown. We performed this study to evaluate the prognostic significance of the GPS in DLBCL in China. We retrospectively analyzed 160 patients with newly diagnosed DLBCL at the Shanghai Ruijin Hospital (China). The prognostic value of the GPS was evaluated and compared with that of the International Prognostic Index (IPI) and immunohistochemical subtyping. The GPS was defined as follows: GPS-0, C-reactive protein (CRP) ≤10 mg/L and albumin ≥35 g/L; GPS-1, CRP >10 mg/L or albumin <35 g/L; and GPS-2, CRP >10 mg/L and albumin <35 g/L. Patients with lower GPS tended to have better outcomes including progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS and high IPI score were independent adverse predictors of OS. Similar to several other tumors, GPS is a reliable predictor of survival outcomes in DLBCL patients treated with R-CHOP therapy. Inflammatory responses are implicated in the progression and survival of patients with DLBCL.

Prognostic Value of the Apparent Diffusion Coefficient in Newborns with Hypoxic-Ischaemic Encephalopathy Treated with Therapeutic Hypothermia.

PubMed

Heursen, Eva-Marie; Zuazo Ojeda, Amaya; Benavente Fernández, Isabel; Jimenez Gómez, Gema; Campuzano Fernández-Colima, Rosalía; Paz-Expósito, José; Lubián López, Simón Pedro

2017-01-01

Apparent diffusion coefficient (ADC) quantification has been proven to be of prognostic value in term newborns with hypoxic-ischaemic encephalopathy (HIE) who were treated under normothermia. To evaluate the prognostic value of ADC in standardized brain regions in neonates with HIE who were treated with therapeutic hypothermia (TH). This prospective cohort study included 54 term newborns who were admitted with HIE and treated with TH. All magnetic resonance imaging examinations were performed between days 4 and 6 of life, and ADC values were measured in 13 standardized regions of the brain. At 2 years of age we explored whether ADC values were related to composite outcomes (death or survival with abnormal neurodevelopment). The severity of HIE is inversely related to ADC values in different brain regions. We found that lower ADC values in the posterior limb of the internal capsule (PLIC), the thalami, the semioval centre, and frontal and parietal white matter were related to adverse outcomes. ADC values in the PLIC and thalami are good predictors of adverse outcomes (AUC 0.86 and 0.76). Low ADC values in the PLIC, thalamus, semioval centre, and frontal and parietal white matter in full-term infants with HIE treated with TH were associated with a poor outcome. © 2017 S. Karger AG, Basel.

Model-Based Prognostics of Hybrid Systems

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Roychoudhury, Indranil; Bregon, Anibal

2015-01-01

Model-based prognostics has become a popular approach to solving the prognostics problem. However, almost all work has focused on prognostics of systems with continuous dynamics. In this paper, we extend the model-based prognostics framework to hybrid systems models that combine both continuous and discrete dynamics. In general, most systems are hybrid in nature, including those that combine physical processes with software. We generalize the model-based prognostics formulation to hybrid systems, and describe the challenges involved. We present a general approach for modeling hybrid systems, and overview methods for solving estimation and prediction in hybrid systems. As a case study, we consider the problem of conflict (i.e., loss of separation) prediction in the National Airspace System, in which the aircraft models are hybrid dynamical systems.

Percutaneous Endoscopic Gastrostomy Tube Is a Negative Prognostic Factor for Recurrent/Metastatic Head and Neck Cancer.

PubMed

Siano, Marco; Jarisch, Nadine; Joerger, Markus; Espeli, Vittoria

2018-06-01

Recurrent/metastatic head and neck squamous cell cancer (r/mHNSCC) patients often need a percutaneous endoscopic gastrostomy feeding tube (PEG). Among known prognostic factors, PEG could be prognostic as well. We retrospectively analyzed r/mHNSCC patients referred for systemic treatment. Kaplan-Meier and multivariate cox regression models were applied to assess prognostic impact of PEG. One hunderd and ten patients were identified, 42 had a PEG at treatment start. Median survival from start of 1st-line systemic treatment was 8 months (95%CI=6.5-12.0 months), 4.5 months (95%CI=2.5-7.0 months) for patients with PEG and 11.5 months (95%CI=7.5-14.5 months) without PEG (adjusted HR=1.98, p=0.011). Similarly, survival from first recurrence of distant metastases was lower in patients with PEG as compared to patients without (7.5 vs. 15.5 months, adjusted HR=2.60, p<0.001). Presence of PEG feeding tube has an unfavourable prognostic impact on survival in patients with r/mHNSCC. While any causality remains speculative, potential complications should be appreciated before PEG implantation. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Distributed Prognostic Health Management with Gaussian Process Regression

NASA Technical Reports Server (NTRS)

Saha, Sankalita; Saha, Bhaskar; Saxena, Abhinav; Goebel, Kai Frank

2010-01-01

Distributed prognostics architecture design is an enabling step for efficient implementation of health management systems. A major challenge encountered in such design is formulation of optimal distributed prognostics algorithms. In this paper. we present a distributed GPR based prognostics algorithm whose target platform is a wireless sensor network. In addition to challenges encountered in a distributed implementation, a wireless network poses constraints on communication patterns, thereby making the problem more challenging. The prognostics application that was used to demonstrate our new algorithms is battery prognostics. In order to present trade-offs within different prognostic approaches, we present comparison with the distributed implementation of a particle filter based prognostics for the same battery data.

Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study.

PubMed

Nickolas, Thomas L; Schmidt-Ott, Kai M; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C; Barasch, Jonathan

2012-01-17

This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The Prognostic Value of Late Gadolinium-Enhanced Cardiac Magnetic Resonance Imaging in Nonischemic Dilated Cardiomyopathy: A Review and Meta-Analysis.

PubMed

Becker, Marthe A J; Cornel, Jan H; van de Ven, Peter M; van Rossum, Albert C; Allaart, Cornelis P; Germans, Tjeerd

2018-04-13

This review and meta-analysis reviews the prognostic value of cardiac magnetic resonance (CMR) in nonischemic dilated cardiomyopathy (DCM). Late gadolinium-enhanced (LGE) CMR is a noninvasive method to determine the underlying cause of DCM and previous studies reported the prognostic value of the presence of LGE to identify patients at risk of major adverse cardiovascular events. PubMed was searched for studies describing the prognostic implication of LGE in patients with DCM for the specified endpoints cardiovascular mortality, major ventricular arrhythmic events including appropriate implantable cardioverter-defibrillator therapy, rehospitalization for heart failure, and left ventricular reverse remodeling. Data from 34 studies were included, with a total of 4,554 patients. Contrast enhancement was present in 44.8% of DCM patients. Patients with LGE had increased cardiovascular mortality (odds ratio [OR]: 3.40; 95% confidence interval [CI]: 2.04 to 5.67), ventricular arrhythmic events (OR: 4.52; 95% CI: 3.41 to 5.99), and rehospitalization for heart failure (OR: 2.66; 95% CI: 1.67 to 4.24) compared with those without LGE. Moreover, the absence of LGE predicted left ventricular reverse remodeling (OR: 0.15; 95% CI: 0.06 to 0.36). The presence of LGE on CMR substantially worsens prognosis for adverse cardiovascular events in DCM patients, and the absence indicates left ventricular reverse remodeling. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Childhood Adversities and Adult Cardiometabolic Health: Does the Quantity, Timing, and Type of Adversity Matter?

PubMed Central

Friedman, Esther M.; Montez, Jennifer Karas; Sheehan, Connor McDevitt; Guenewald, Tara L.; Seeman, Teresa E.

2015-01-01

Objective Adverse events in childhood can indelibly influence adult health. While evidence for this association has mounted, a fundamental set of questions about how to operationalize adverse events has been understudied. Method We used data from the National Survey of Midlife Development in the United States to examine how quantity, timing, and types of adverse events in childhood are associated with adult cardiometabolic health. Results The best-fitting specification of quantity of events was a linear measure reflecting a dose–response relationship. Timing of event mattered less than repeated exposure to events. Regarding the type of event, academic interruptions and sexual/physical abuse were most important. Adverse childhood events elevated the risk of diabetes and obesity similarly for men and women but had a greater impact on women’s risk of heart disease. Discussion Findings demonstrate the insights that can be gleaned about the early-life origins of adult health by examining operationalization of childhood exposures. PMID:25903978

Residual tumor after neoadjuvant chemoradiation outside the radiation therapy target volume: a new prognostic factor for survival in esophageal cancer.

PubMed

Muijs, Christina; Smit, Justin; Karrenbeld, Arend; Beukema, Jannet; Mul, Veronique; van Dam, Go; Hospers, Geke; Kluin, Phillip; Langendijk, Johannes; Plukker, John

2014-03-15

The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities. Copyright © 2014 Elsevier Inc. All rights reserved.

Interpretative variability and its impact on the prognostic value of myocardial fatty acid imaging in asymptomatic hemodialysis patients in a multicenter trial in Japan.

PubMed

Kiriyama, Tomonari; Kumita, Shin-Ichiro; Moroi, Masao; Nishimura, Tsunehiko; Tamaki, Nagara; Hasebe, Naoyuki; Kikuchi, Kenjiro

2015-01-01

The severity of impaired fatty acid utilization in the myocardium can predict cardiac death in asymptomatic patients on hemodialysis. However, interpretive variability and its impact on the prognostic value of myocardial fatty acid imaging are unknown. A total of 677 patients who received hemodialysis for ≥ 20 years and had one or more cardiovascular risk factors underwent (123)I-labeled β-methyl iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) at 48 hospitals across Japan. SPECT images were interpreted by experts at the nuclear core laboratory and by readers with varying skill levels at clinical centers, based on the standard 17-segment model and 5-point scoring systems, independently. The κ values only reached fair agreement both for overall impression (κ=0.298, normal vs. abnormal) and for categorical impression (κ=0.244, normal vs. mildly abnormal vs. severely abnormal). The normalcy rate was lower in readers at the clinical centers (60.9%) than in experts (69.9%). In contrast to the results assessed by experts, a Kaplan-Meier analysis based on the interpretation by readers at the clinical centers failed to distinguish the risk of events in patients with normal scans from that of patients with mildly abnormal scans. Considerable variability and its impact on prognostic value were observed in the visual interpretation of BMIPP SPECT images between experts and readers at the clinical centers.

Financial impact of inaccurate Adverse Event recording post Hip Fracture surgery: Addendum to 'Adverse event recording post hip fracture surgery'.

PubMed

Lee, Matthew J; Doody, Kevin; Mohamed, Khalid M S; Butler, Audrey; Street, John; Lenehan, Brian

2018-02-15

A study in 2011 by (Doody et al. Ir Med J 106(10):300-302, 2013) looked at comparing inpatient adverse events recorded prospectively at the point of care, with adverse events recorded by the national Hospital In-Patient Enquiry (HIPE) System. In the study, a single-centre University Hospital in Ireland treating acute hip fractures in an orthopaedic unit recorded 39 patients over a 2-month (August-September 2011) period, with 55 adverse events recorded prospectively in contrast to the HIPE record of 13 (23.6%) adverse events. With the recent change in the Irish hospital funding model from block grant to an 'activity-based funding' on the basis of case load and case complexity, the hospital financial allocation is dependent on accurate case complexity coding. A retrospective assessment of the financial implications of the two methods of adverse incident recording was carried out. A total of €39,899 in 'missed funding' for 2 months was calculated when the ward-based, prospectively collected data was compared to the national HIPE data. Accurate data collection is paramount in facilitating activity-based funding, to improve patient care and ensure the appropriate allocation of resources.

Prognostic model for survival in patients with early stage cervical cancer.

PubMed

Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

2011-02-15

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

Adverse childhood experience and asthma onset: a systematic review.

PubMed

Exley, Daniel; Norman, Alyson; Hyland, Michael

2015-06-01

Adverse childhood experiences such as abuse and neglect are associated with subsequent immune dysregulation. Some studies show an association between adverse childhood experiences and asthma onset, although significant disparity in results exists in the published literature. We aimed to review available studies employing a prospective design that investigates associations between adverse childhood experience and asthma. A search protocol was developed and studies were drawn from four electronic journal databases. Studies were selected in accordance with pre-set inclusion criteria and relevant data were extracted. 12 studies, assessing data from a total of 31 524 individuals, were identified that investigate the impact of a range of adverse childhood experiences on the likelihood of developing asthma. Evidence suggests that chronic stress exposure and maternal distress in pregnancy operate synergistically with known triggers such as traffic-related air pollution to increase asthma risk. Chronic stress in early life is associated with an increased risk of asthma onset. There is evidence that adverse childhood experience increases the impact of traffic-related air pollution and inconsistent evidence that adverse childhood experience has an independent effect on asthma onset. Copyright ©ERS 2015.

Prognostic value of inflammation-based scores in patients with osteosarcoma

PubMed Central

Liu, Bangjian; Huang, Yujing; Sun, Yuanjue; Zhang, Jianjun; Yao, Yang; Shen, Zan; Xiang, Dongxi; He, Aina

2016-01-01

Systemic inflammation responses have been associated with cancer development and progression. C-reactive protein (CRP), Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score (NPS) have been shown to be independent risk factors in various types of malignant tumors. This retrospective analysis of 162 osteosarcoma cases was performed to estimate their predictive value of survival in osteosarcoma. All statistical analyses were performed by SPSS statistical software. Receiver operating characteristic (ROC) analysis was generated to set optimal thresholds; area under the curve (AUC) was used to show the discriminatory abilities of inflammation-based scores; Kaplan-Meier analysis was performed to plot the survival curve; cox regression models were employed to determine the independent prognostic factors. The optimal cut-off points of NLR, PLR, and LMR were 2.57, 123.5 and 4.73, respectively. GPS and NLR had a markedly larger AUC than CRP, PLR and LMR. High levels of CRP, GPS, NLR, PLR, and low level of LMR were significantly associated with adverse prognosis (P < 0.05). Multivariate Cox regression analyses revealed that GPS, NLR, and occurrence of metastasis were top risk factors associated with death of osteosarcoma patients. PMID:28008988

Prognostic Factors and Expression of MDM2 in Patients with Primary Extremity Liposarcoma

PubMed Central

Júnior, Rosalvo Zósimo Bispo; de Camargo, Olavo Pires; de Oliveira, Cláudia Regina G. C. M.; Filippi, Renée Zon; Baptista, André Mathias; Caiero, Marcelo Tadeu

2008-01-01

OBJECTIVE The objective of this study was to investigate MDM2 (murine double minute 2) protein expression and evaluate its relationship with some anatomical and pathological aspects, aiming also to identify prognostic factors concerning local recurrence-free survival, metastasis-free survival and overall survival in patients with primary liposarcomas of the extremities. MATERIALS AND METHODS Of 50 patients with primary liposarcomas of the extremities admitted to a Reference Service, between 1968 and 2004, 25 were enrolled in the study, following eligibility and exclusion criteria. RESULTS The adverse factors that influenced the risk for local recurrence in the univariant analysis included male sex (P = 0.023), pleomorphic histological subtype (P = 0.027), and high histological grade (P = 0.007). Concerning metastasis-free survival, age less than 50 years (P = 0.040), male sex (P = 0.040), pleomorphic subtype (P < 0.001), and high histological grade (P = 0.003) had a worse prognosis. Adverse factors for overall survival were age under 50 years (P = 0.040), male sex (P = 0.040), pleomorphic subtype (P < 0.001), and high histological grade (P = 0.003). CONCLUSIONS There was no correlation between immunohistochemically observed MDM2 protein expressions and the anatomical and pathological variables studied. The immunohistochemical expression of MDM2 protein was not considered to have a prognostic value for any of the surviving patients in this study (local recurrence-free survival, metastasis-free survival, or overall survival). The immunoexpression of MDM2 protein was a frequent event in the different subtypes of liposarcomas. PMID:18438568

Impact of Elevated End-Diastolic Pulmonary Regurgitation Gradient on Worse Clinical Outcomes in Hospitalized Patients With Heart Failure.

PubMed

Honda, Yasuyuki; Nagai, Toshiyuki; Sugano, Yasuo; Honda, Satoshi; Okada, Atsushi; Asaumi, Yasuhide; Aiba, Takeshi; Noguchi, Teruo; Kusano, Kengo; Ogawa, Hisao; Yasuda, Satoshi; Anzai, Toshihisa

2017-02-15

The echo Doppler end-diastolic pulmonary regurgitation (EDPR) gradient correlates well with catheter-derived pulmonary artery diastolic pressure. An elevated EDPR gradient is associated with worse clinical outcomes in patients with stable coronary artery disease. However, the prognostic significance of EDPR gradient in patients with heart failure (HF) is unclear. The aim of the present study was to investigate the prognostic impact of EDPR gradient in HF. We retrospectively examined 751 consecutive hospitalized patients with acute HF. Those with acute coronary syndrome or in-hospital death and those without accessible EDPR gradient data at discharge were excluded. Finally, 265 patients were examined and divided into 2 groups according to EDPR gradient (cutoff 9 mm Hg). Adverse events were defined as worsening HF and death. Patients with elevated EDPR gradient had higher B-type natriuretic peptide, lower age, and lower left ventricular ejection fraction at discharge than those with nonelevated EDPR gradient. During a median follow-up of 429 days, elevated EDPR gradient was independently associated with adverse events (hazard ratio 2.34, 95% CI 1.44 to 3.78, p <0.001) after adjustment for confounders. In conclusion, echo Doppler EDPR gradient might be a noninvasive predictor of clinical outcomes in hospitalized patients with HF. Copyright © 2016 Elsevier Inc. All rights reserved.

[Biases in the study of prognostic factors].

PubMed

Delgado-Rodríguez, M

1999-01-01

The main objective is to detail the main biases in the study of prognostic factors. Confounding bias is illustrated with social class, a prognostic factor still discussed. Within selection bias several cases are commented: response bias, specially frequent when the patients of a clinical trial are used; the shortcomings in the formation of an inception cohort; the fallacy of Neyman (bias due to the duration of disease) when the study begins with a cross-sectional study; the selection bias in the treatment of survivors for the different treatment opportunity of those living longer; the bias due to the inclusion of heterogeneous diagnostic groups; and the selection bias due to differential information losses and the use of statistical multivariate procedures. Within the biases during follow-up, an empiric rule to value the impact of the number of losses is given. In information bias the Will Rogers' phenomenon and the usefulness of clinical databases are discussed. Lastly, a recommendation against the use of cutoff points yielded by bivariate analyses to select the variable to be included in multivariate analysis is given.

Prognostication of Learning Curve on Surgical Management of Vasculobiliary Injuries after Cholecystectomy

PubMed Central

Dar, Faisal Saud; Zia, Haseeb; Rafique, Muhammad Salman; Khan, Nusrat Yar; Salih, Mohammad; Hassan Shah, Najmul

2016-01-01

Background. Concomitant vascular injury might adversely impact outcomes after iatrogenic bile duct injury (IBDI). Whether a new HPB center should embark upon repair of complex biliary injuries with associated vascular injuries during learning curve is unknown. The objective of this study was to determine outcome of surgical management of IBDI with and without vascular injuries in a new HPB center during its learning curve. Methods. We retrospectively reviewed patients who underwent surgical management of IBDI at our center. A total of 39 patients were included. Patients without (Group 1) and with vascular injuries (Group 2) were compared. Outcome was defined as 90-day morbidity and mortality. Results. Median age was 39 (20–80) years. There were 10 (25.6%) vascular injuries. E2 injuries were associated significantly with high frequency of vascular injuries (66% versus 15.1%) (P = 0.01). Right hepatectomy was performed in three patients. Out of these, two had a right hepatic duct stricture and one patient had combined right arterial and portal venous injury. The number of patients who developed postoperative complications was not significantly different between the two groups (11.1% versus 23.4%) (P = 0.6). Conclusion. Learning curve is not a negative prognostic variable in the surgical management of iatrogenic vasculobiliary injuries after cholecystectomy. PMID:27525124

A framework for quantifying net benefits of alternative prognostic models.

PubMed

Rapsomaniki, Eleni; White, Ian R; Wood, Angela M; Thompson, Simon G

2012-01-30

New prognostic models are traditionally evaluated using measures of discrimination and risk reclassification, but these do not take full account of the clinical and health economic context. We propose a framework for comparing prognostic models by quantifying the public health impact (net benefit) of the treatment decisions they support, assuming a set of predetermined clinical treatment guidelines. The change in net benefit is more clinically interpretable than changes in traditional measures and can be used in full health economic evaluations of prognostic models used for screening and allocating risk reduction interventions. We extend previous work in this area by quantifying net benefits in life years, thus linking prognostic performance to health economic measures; by taking full account of the occurrence of events over time; and by considering estimation and cross-validation in a multiple-study setting. The method is illustrated in the context of cardiovascular disease risk prediction using an individual participant data meta-analysis. We estimate the number of cardiovascular-disease-free life years gained when statin treatment is allocated based on a risk prediction model with five established risk factors instead of a model with just age, gender and region. We explore methodological issues associated with the multistudy design and show that cost-effectiveness comparisons based on the proposed methodology are robust against a range of modelling assumptions, including adjusting for competing risks. Copyright © 2011 John Wiley & Sons, Ltd.

A framework for quantifying net benefits of alternative prognostic models‡

PubMed Central

Rapsomaniki, Eleni; White, Ian R; Wood, Angela M; Thompson, Simon G

2012-01-01

New prognostic models are traditionally evaluated using measures of discrimination and risk reclassification, but these do not take full account of the clinical and health economic context. We propose a framework for comparing prognostic models by quantifying the public health impact (net benefit) of the treatment decisions they support, assuming a set of predetermined clinical treatment guidelines. The change in net benefit is more clinically interpretable than changes in traditional measures and can be used in full health economic evaluations of prognostic models used for screening and allocating risk reduction interventions. We extend previous work in this area by quantifying net benefits in life years, thus linking prognostic performance to health economic measures; by taking full account of the occurrence of events over time; and by considering estimation and cross-validation in a multiple-study setting. The method is illustrated in the context of cardiovascular disease risk prediction using an individual participant data meta-analysis. We estimate the number of cardiovascular-disease-free life years gained when statin treatment is allocated based on a risk prediction model with five established risk factors instead of a model with just age, gender and region. We explore methodological issues associated with the multistudy design and show that cost-effectiveness comparisons based on the proposed methodology are robust against a range of modelling assumptions, including adjusting for competing risks. Copyright © 2011 John Wiley & Sons, Ltd. PMID:21905066

Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases.

PubMed

Reilly, J T; Snowden, J A; Spearing, R L; Fitzgerald, P M; Jones, N; Watmore, A; Potter, A

1997-07-01

The prognostic significance of cytogenetic abnormalities was determined in 106 patients with well-characterized idiopathic myelofibrosis who were successfully karyotyped at diagnosis. 35% of the cases exhibited a clonal abnormality (37/106), whereas 65% (69/106) had a normal karyotype. Three characteristic defects, namely del(13q) (nine cases), del(20q) (eight cases) and partial trisomy 1q (seven cases), were present in 64.8% (24/37) of patients with clonal abnormalities. Kaplan-Meier plots and log rank analysis demonstrated an abnormal karyotype to be an adverse prognostic variable (P<0.001). Of the eight additional clinical and haematological parameters recorded at diagnosis, age (P<0.01), anaemia (haemoglobin < or = 10 g/dl: P<0.001), platelet (< or = 100 x 10(9)/l, P<0.0001) and leucocyte count (> 10.3 x 10(9)/l; P=0.06) were also associated with a shorter survival. In contrast, sex, spleen and liver size, and percentage blast cells were not found to be significant. Multivariate analysis, using Cox's regression, revealed karyotype, haemoglobin concentration, platelet and leucocyte counts to retain their unfavourable prognostic significance. A simple and useful schema for predicting survival in idiopathic myelofibrosis has been produced by combining age, haemoglobin concentration and karyotype with median survival times varying from 180 months (good-risk group) to 16 months (poor-risk group).

High truncated-O-glycan score predicts adverse clinical outcome in patients with localized clear-cell renal cell carcinoma after surgery.

PubMed

NguyenHoang, SonTung; Liu, Yidong; Xu, Le; Zhou, Lin; Chang, Yuan; Fu, Qiang; Liu, Zheng; Lin, Zongming; Xu, Jiejie

2017-10-03

Truncated O-glycans, including Tn-antigen, sTn-antigen, T-antigen, sT-antigen, are incomplete glycosylated structures and their expression occur frequently in tumor tissue. The study aims to evaluate the abundance of each truncated O-glycans and its clinical significance in postoperative patients with localized clear-cell renal cell carcinoma (ccRCC). We used immunohistochemical testing to analyze the expression of truncated O-glycans in tumor specimens from 401 patients with localized ccRCC. Truncated-O-glycan score was built by integrating the expression level of Tn-, sTn- and sT-antigen. Kaplan-Meier survival and Cox regression analysis were done to compare clinical outcomes in subgroups. Receiver operating characteristic (ROC) was applied to assess the impact of prognostic factors on overall survival (OS) and recurrence-free survival (RFS). The results identified Tn-, sTn-, sT-antigen as independent prognosticators. The OS and RFS were shortened among the 198 (49.4%) patients with high Truncated-O-glycan score than among the 203 (50.6%) patients with low score (hazard ratio for OS, 7.060; 95% confidence interval [CI]: 2.765 to 18.027; p <0.001; for RFS, 4.612; 95% CI: 2.141 to 9.931; p <0.001). There is no difference between low-risk patients and high-risk patients in low score group ( p = 0.987). High-risk patients with low score showed a better prognosis than low-risk patient with high score ( p = 0.029). The Truncated-O-glycan score showed better prognostic value for OS (AUC: 0.739, p = 0.003) and RFS (AUC: 0.719, p = 0.003) than TNM stage. In summary, the high Truncated-O-glycan score could predict adverse clinical outcome in localized ccRCC patients after surgery.

Evaluation of prognostic models developed using standardised image features from different PET automated segmentation methods.

PubMed

Parkinson, Craig; Foley, Kieran; Whybra, Philip; Hills, Robert; Roberts, Ashley; Marshall, Chris; Staffurth, John; Spezi, Emiliano

2018-04-11

Prognosis in oesophageal cancer (OC) is poor. The 5-year overall survival (OS) rate is approximately 15%. Personalised medicine is hoped to increase the 5- and 10-year OS rates. Quantitative analysis of PET is gaining substantial interest in prognostic research but requires the accurate definition of the metabolic tumour volume. This study compares prognostic models developed in the same patient cohort using individual PET segmentation algorithms and assesses the impact on patient risk stratification. Consecutive patients (n = 427) with biopsy-proven OC were included in final analysis. All patients were staged with PET/CT between September 2010 and July 2016. Nine automatic PET segmentation methods were studied. All tumour contours were subjectively analysed for accuracy, and segmentation methods with < 90% accuracy were excluded. Standardised image features were calculated, and a series of prognostic models were developed using identical clinical data. The proportion of patients changing risk classification group were calculated. Out of nine PET segmentation methods studied, clustering means (KM2), general clustering means (GCM3), adaptive thresholding (AT) and watershed thresholding (WT) methods were included for analysis. Known clinical prognostic factors (age, treatment and staging) were significant in all of the developed prognostic models. AT and KM2 segmentation methods developed identical prognostic models. Patient risk stratification was dependent on the segmentation method used to develop the prognostic model with up to 73 patients (17.1%) changing risk stratification group. Prognostic models incorporating quantitative image features are dependent on the method used to delineate the primary tumour. This has a subsequent effect on risk stratification, with patients changing groups depending on the image segmentation method used.

Assessing Stress-Related Treatment Needs among Girls at Risk for Poor Functional Outcomes: The Impact of Cumulative Adversity, Criterion Traumas, and Non-Criterion Events

PubMed Central

Lansing, Amy E.; Plante, Wendy Y.; Beck, Audrey N.

2016-01-01

Despite growing recognition that cumulative adversity (total stressor exposure), including complex trauma, increases the risk for psychopathology and impacts development, assessment strategies lag behind: Trauma-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (parental separations) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: 1) an average of 14 adverse Criterion-A and non-Criterion event exposures; 2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; 3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and 4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. PMID:27745922

The prognostic impact of in-hospital worsening of renal function in patients with acute coronary syndrome.

PubMed

AlFaleh, Hussam F; Alsuwaida, Abdulkareem O; Ullah, Anhar; Hersi, Ahmad; AlHabib, Khalid F; AlNemer, Khalid; AlSaif, Shukri; Taraben, Amir; Kashour, Tarek; Balghith, Mohammed A; Ahmed, Waqar H

2013-08-10

Renal impairment is strongly linked to adverse cardiovascular (CV) events. Baseline renal dysfunction is a strong predictor of CV mortality and morbidity in patients admitted with acute coronary syndrome (ACS). However, the prognostic importance of worsening renal function (WRF) in these patients is not well characterized. ACS patients enrolled in the SPACE (Saudi Project for Assessment of Coronary Events) registry who had baseline and pre-discharge serum creatinine data available were eligible for this study. WRF was defined as a 25% reduction from admission estimated glomerular filtration rate (eGFR) within 7 days of hospitalization. Baseline demographics, clinical presentation, therapies, and in-hospital outcomes were compared. Of the 3583 ACS patients, WRF occurred in 225 patients (6.3%), who were older, had more cardiovascular risk factors, were more likely to be female, have past vascular disease, and presented with more non-ST-segment elevation myocardial infarction than patients without WRF (39.5% vs. 32.8%; p=0.042). WRF was associated with an increased risk of in-hospital death, heart failure, cardiogenic shock, and stroke. After adjusting for potential confounders, WRF was an independent predictor of in-hospital death (adjusted odd ratio 28.02, 95% CI 13.2-60.28, p<0.0001). WRF was more predictive of mortality than baseline eGFR. These results indicate that WRF is a powerful predictor for in-hospital mortality and CV complications in ACS patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Assessing stress-related treatment needs among girls at risk for poor functional outcomes: The impact of cumulative adversity, criterion traumas, and non-criterion events.

PubMed

Lansing, Amy E; Plante, Wendy Y; Beck, Audrey N

2017-05-01

Despite growing recognition that cumulative adversity (total stressor exposure, including complex trauma), increases the risk for psychopathology and impacts development, assessment strategies lag behind: Adversity-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A traumatic event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (separation from caregivers) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: (1) an average of 14 adverse Criterion-A and non-Criterion event exposures; (2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; (3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and (4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. Copyright © 2016 Elsevier Ltd. All rights reserved.

State of the art and taxonomy of prognostics approaches, trends of prognostics applications and open issues towards maturity at different technology readiness levels

NASA Astrophysics Data System (ADS)

Javed, Kamran; Gouriveau, Rafael; Zerhouni, Noureddine

2017-09-01

Integrating prognostics to a real application requires a certain maturity level and for this reason there is a lack of success stories about development of a complete Prognostics and Health Management system. In fact, the maturity of prognostics is closely linked to data and domain specific entities like modeling. Basically, prognostics task aims at predicting the degradation of engineering assets. However, practically it is not possible to precisely predict the impending failure, which requires a thorough understanding to encounter different sources of uncertainty that affect prognostics. Therefore, different aspects crucial to the prognostics framework, i.e., from monitoring data to remaining useful life of equipment need to be addressed. To this aim, the paper contributes to state of the art and taxonomy of prognostics approaches and their application perspectives. In addition, factors for prognostics approach selection are identified, and new case studies from component-system level are discussed. Moreover, open challenges toward maturity of the prognostics under uncertainty are highlighted and scheme for an efficient prognostics approach is presented. Finally, the existing challenges for verification and validation of prognostics at different technology readiness levels are discussed with respect to open challenges.

Explaining the black-white gap in cognitive test scores: Toward a theory of adverse impact.

PubMed

Cottrell, Jonathan M; Newman, Daniel A; Roisman, Glenn I

2015-11-01

In understanding the causes of adverse impact, a key parameter is the Black-White difference in cognitive test scores. To advance theory on why Black-White cognitive ability/knowledge test score gaps exist, and on how these gaps develop over time, the current article proposes an inductive explanatory model derived from past empirical findings. According to this theoretical model, Black-White group mean differences in cognitive test scores arise from the following racially disparate conditions: family income, maternal education, maternal verbal ability/knowledge, learning materials in the home, parenting factors (maternal sensitivity, maternal warmth and acceptance, and safe physical environment), child birth order, and child birth weight. Results from a 5-wave longitudinal growth model estimated on children in the NICHD Study of Early Child Care and Youth Development from ages 4 through 15 years show significant Black-White cognitive test score gaps throughout early development that did not grow significantly over time (i.e., significant intercept differences, but not slope differences). Importantly, the racially disparate conditions listed above can account for the relation between race and cognitive test scores. We propose a parsimonious 3-Step Model that explains how cognitive test score gaps arise, in which race relates to maternal disadvantage, which in turn relates to parenting factors, which in turn relate to cognitive test scores. This model and results offer to fill a need for theory on the etiology of the Black-White ethnic group gap in cognitive test scores, and attempt to address a missing link in the theory of adverse impact. (c) 2015 APA, all rights reserved).

MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

PubMed Central

Valera, Alexandra; López-Guillermo, Armando; Cardesa-Salzmann, Teresa; Climent, Fina; González-Barca, Eva; Mercadal, Santiago; Espinosa, Íñigo; Novelli, Silvana; Briones, Javier; Mate, José L.; Salamero, Olga; Sancho, Juan M.; Arenillas, Leonor; Serrano, Sergi; Erill, Nadina; Martínez, Daniel; Castillo, Paola; Rovira, Jordina; Martínez, Antonio; Campo, Elias; Colomo, Luis

2013-01-01

MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rearrangements (MYC double/triple-hit) in 4%, MYC amplifications in 2% and MYC gains in 19%. MYC single-hit, MYC double/triple-hit and MYC amplifications, but not MYC gains or other gene rearrangements, were associated with unfavorable progression-free survival and overall survival. MYC protein expression, evaluated using computerized image analysis, captured the unfavorable prognosis of MYC translocations/amplifications and identified an additional subset of patients without gene alterations but with similar poor prognosis. Patients with tumors expressing both MYC/BCL2 had the worst prognosis, whereas those with double-negative tumors had the best outcome. High MYC expression was associated with shorter overall survival irrespectively of the International Prognostic Index and BCL2 expression. In conclusion, MYC protein expression identifies a subset of diffuse large B-cell lymphoma with very poor prognosis independently of gene alterations and other prognostic parameters. PMID:23716551

MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

PubMed

Valera, Alexandra; López-Guillermo, Armando; Cardesa-Salzmann, Teresa; Climent, Fina; González-Barca, Eva; Mercadal, Santiago; Espinosa, Iñigo; Novelli, Silvana; Briones, Javier; Mate, José L; Salamero, Olga; Sancho, Juan M; Arenillas, Leonor; Serrano, Sergi; Erill, Nadina; Martínez, Daniel; Castillo, Paola; Rovira, Jordina; Martínez, Antonio; Campo, Elias; Colomo, Luis

2013-10-01

MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rearrangements (MYC double/triple-hit) in 4%, MYC amplifications in 2% and MYC gains in 19%. MYC single-hit, MYC double/triple-hit and MYC amplifications, but not MYC gains or other gene rearrangements, were associated with unfavorable progression-free survival and overall survival. MYC protein expression, evaluated using computerized image analysis, captured the unfavorable prognosis of MYC translocations/amplifications and identified an additional subset of patients without gene alterations but with similar poor prognosis. Patients with tumors expressing both MYC/BCL2 had the worst prognosis, whereas those with double-negative tumors had the best outcome. High MYC expression was associated with shorter overall survival irrespectively of the International Prognostic Index and BCL2 expression. In conclusion, MYC protein expression identifies a subset of diffuse large B-cell lymphoma with very poor prognosis independently of gene alterations and other prognostic parameters.

On Applying the Prognostic Performance Metrics

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

2009-01-01

Prognostics performance evaluation has gained significant attention in the past few years. As prognostics technology matures and more sophisticated methods for prognostic uncertainty management are developed, a standardized methodology for performance evaluation becomes extremely important to guide improvement efforts in a constructive manner. This paper is in continuation of previous efforts where several new evaluation metrics tailored for prognostics were introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. Several shortcomings identified, while applying these metrics to a variety of real applications, are also summarized along with discussions that attempt to alleviate these problems. Further, these metrics have been enhanced to include the capability of incorporating probability distribution information from prognostic algorithms as opposed to evaluation based on point estimates only. Several methods have been suggested and guidelines have been provided to help choose one method over another based on probability distribution characteristics. These approaches also offer a convenient and intuitive visualization of algorithm performance with respect to some of these new metrics like prognostic horizon and alpha-lambda performance, and also quantify the corresponding performance while incorporating the uncertainty information.

Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival.

PubMed

Eilertsen, Marte; Andersen, Sigve; Al-Saad, Samer; Kiselev, Yury; Donnem, Tom; Stenvold, Helge; Pettersen, Ingvild; Al-Shibli, Khalid; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy M

2014-01-01

Monocarboxylate transporters (MCTs) 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC. Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4. In univariate analyses; ↓ MCT1 (P = 0.021) and ↑ MCT4 (P = 0.027) expression in cancer cells, and ↑ MCT1 (P = 0.003), ↓ MCT2 (P = 0.006), ↓ MCT3 (P = 0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001), ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001), ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031) and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016) were significant independent poor prognostic markers for DSS. We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.

Weight-of-evidence evaluation of an adverse outcome ...

EPA Pesticide Factsheets

Ongoing honey bee colony losses are of significant international concern because of the essential role these insects play in pollinating staple food crops. Chemical and non-chemical stressors both have been implicated as possible contributors to colony failure, however, the potential role of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptor (nAChR) to eliminate target pest insects, however, mounting evidence indicates that these chemicals may adversely affect beneficial pollinators, such as the honey bee, via impacts on learning and memory thereby affecting foraging success. However, the mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. Therefore, the objective of this work was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between the nAChR and colony level impacts. Development of these AOPs has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect honey bee health, causing colony instability and further failure. From this effort, an AOP network also was developed, laying the f

The Sensitivity of Adverse Event Cost Estimates to Diagnostic Coding Error

PubMed Central

Wardle, Gavin; Wodchis, Walter P; Laporte, Audrey; Anderson, Geoffrey M; Baker, Ross G

2012-01-01

Objective To examine the impact of diagnostic coding error on estimates of hospital costs attributable to adverse events. Data Sources Original and reabstracted medical records of 9,670 complex medical and surgical admissions at 11 hospital corporations in Ontario from 2002 to 2004. Patient specific costs, not including physician payments, were retrieved from the Ontario Case Costing Initiative database. Study Design Adverse events were identified among the original and reabstracted records using ICD10-CA (Canadian adaptation of ICD10) codes flagged as postadmission complications. Propensity score matching and multivariate regression analysis were used to estimate the cost of the adverse events and to determine the sensitivity of cost estimates to diagnostic coding error. Principal Findings Estimates of the cost of the adverse events ranged from $16,008 (metabolic derangement) to $30,176 (upper gastrointestinal bleeding). Coding errors caused the total cost attributable to the adverse events to be underestimated by 16 percent. The impact of coding error on adverse event cost estimates was highly variable at the organizational level. Conclusions Estimates of adverse event costs are highly sensitive to coding error. Adverse event costs may be significantly underestimated if the likelihood of error is ignored. PMID:22091908

Prognostic impact of preoperative statin use after radical nephroureterectomy for upper urinary tract urothelial carcinoma

PubMed Central

Lim, Ju Hyun; Jeong, In Gab; Park, Jong Yeon; You, Dalsan; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong

2015-01-01

Purpose The objective was to investigate the impact of statin use on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC). Materials and Methods A retrospective review of medical records identified 277 patients who underwent radical nephroureterectomy for primary UTUC at Asan Medical Center between January 2006 and December 2011. Information on preoperative statin use was obtained from patient charts in an electronic database. We assessed the impact of statin use on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results Of these 277 patients, 62 (22.4%) were taking statin medications. Compared to the statin nonusers, the statin users were older, had a higher body mass index, and had higher rates of cardiovascular disease and diabetes. The 5-year RFS rates of statin users and nonusers were 78.5% and 72.5%, respectively (p=0.528); the 5-year CSS rates were 85.6% and 77.7%, respectively (p=0.516); and the 5-year OS rates were 74.5% and 71.4%, respectively (p=0.945). In the multivariate analysis, statin use was not an independent prognostic factor for RFS (hazard ratio, 0.47; p=0.056), CSS (hazard ratio, 0.46; p=0.093), or OS (hazard ratio, 0.59; p=0.144) in patients who underwent radical nephroureterectomy for UTUC. Conclusions Statin use was not associated with improved RFS, CSS, or OS in the sample population of patients with UTUC. PMID:26175868

Prognostic impact of preoperative statin use after radical nephroureterectomy for upper urinary tract urothelial carcinoma.

PubMed

Lim, Ju Hyun; Jeong, In Gab; Park, Jong Yeon; You, Dalsan; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

2015-07-01

The objective was to investigate the impact of statin use on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC). A retrospective review of medical records identified 277 patients who underwent radical nephroureterectomy for primary UTUC at Asan Medical Center between January 2006 and December 2011. Information on preoperative statin use was obtained from patient charts in an electronic database. We assessed the impact of statin use on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Of these 277 patients, 62 (22.4%) were taking statin medications. Compared to the statin nonusers, the statin users were older, had a higher body mass index, and had higher rates of cardiovascular disease and diabetes. The 5-year RFS rates of statin users and nonusers were 78.5% and 72.5%, respectively (p=0.528); the 5-year CSS rates were 85.6% and 77.7%, respectively (p=0.516); and the 5-year OS rates were 74.5% and 71.4%, respectively (p=0.945). In the multivariate analysis, statin use was not an independent prognostic factor for RFS (hazard ratio, 0.47; p=0.056), CSS (hazard ratio, 0.46; p=0.093), or OS (hazard ratio, 0.59; p=0.144) in patients who underwent radical nephroureterectomy for UTUC. Statin use was not associated with improved RFS, CSS, or OS in the sample population of patients with UTUC.

Annual Research Review: Positive adjustment to adversity -Trajectories of minimal-impact resilience and emergent resilience

PubMed Central

Bonanno, George A.; Diminich, Erica D.

2012-01-01

Background Research on resilience in the aftermath of potentially traumatic life events is still evolving. For decades researchers have documented resilience in children exposed to corrosive early environments, such as poverty or chronic maltreatment. Relatively more recently the study of resilience has migrated to the investigation of isolated and potentially traumatic life events (PTE) in adults. Methods In this article we first consider some of the key differences in the conceptualization of resilience following chronic adversity versus resilience following single-incident traumas, and then describe some of the misunderstandings that have developed about these constructs. To organize our discussion we introduce the terms emergent resilience and minimal-impact resilience to represent trajectories positive adjustment in these two domains, respectively. Results We focused in particular on minimal-impact resilience, and reviewed recent advances in statistical modeling of latent trajectories that have informed the most recent research on minimal-impact resilience in both children and adults and the variables that predict it, including demographic variables, exposure, past and current stressors, resources, personality, positive emotion, coping and appraisal, and flexibility in coping and emotion regulation. Conclusions The research on minimal impact resilience is nascent. Further research is warranted with implications for a multiple levels of analysis approach to elucidate the processes that may mitigate or modify the impact of a PTE at different developmental stages. PMID:23215790

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia.

PubMed

Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stéphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystèle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hélène; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hélène; Leblondon, Véronique

2013-04-01

Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics.

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases--relationships and comparisons with vascular markers of atherosclerosis.

PubMed

Lau, Kui Kai; Wong, Yuen Kwun; Chan, Yap Hang; Teo, Kay Cheong; Chan, Koon Ho; Wai Li, Leonard Sheung; Cheung, Raymond Tak Fai; Siu, Chung Wah; Ho, Shu Leong; Tse, Hung Fat

2014-07-01

Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits. After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P<0.01). BPV significantly correlated with all of the vascular assessments (P<0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69 ± 0.03, P<0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65 ± 0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Multivariate meta-analysis of prognostic factor studies with multiple cut-points and/or methods of measurement.

PubMed

Riley, Richard D; Elia, Eleni G; Malin, Gemma; Hemming, Karla; Price, Malcolm P

2015-07-30

A prognostic factor is any measure that is associated with the risk of future health outcomes in those with existing disease. Often, the prognostic ability of a factor is evaluated in multiple studies. However, meta-analysis is difficult because primary studies often use different methods of measurement and/or different cut-points to dichotomise continuous factors into 'high' and 'low' groups; selective reporting is also common. We illustrate how multivariate random effects meta-analysis models can accommodate multiple prognostic effect estimates from the same study, relating to multiple cut-points and/or methods of measurement. The models account for within-study and between-study correlations, which utilises more information and reduces the impact of unreported cut-points and/or measurement methods in some studies. The applicability of the approach is improved with individual participant data and by assuming a functional relationship between prognostic effect and cut-point to reduce the number of unknown parameters. The models provide important inferential results for each cut-point and method of measurement, including the summary prognostic effect, the between-study variance and a 95% prediction interval for the prognostic effect in new populations. Two applications are presented. The first reveals that, in a multivariate meta-analysis using published results, the Apgar score is prognostic of neonatal mortality but effect sizes are smaller at most cut-points than previously thought. In the second, a multivariate meta-analysis of two methods of measurement provides weak evidence that microvessel density is prognostic of mortality in lung cancer, even when individual participant data are available so that a continuous prognostic trend is examined (rather than cut-points). © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Neutrophil infiltration is a favorable prognostic factor in early stages of colon cancer.

PubMed

Wikberg, Maria L; Ling, Agnes; Li, Xingru; Öberg, Åke; Edin, Sofia; Palmqvist, Richard

2017-10-01

The tumor immune response has been proven critical to prognosis in colorectal cancer (CRC), but studies on the prognostic role of neutrophil infiltration have shown contradictory results. The aim of this study was to elucidate the prognostic role of infiltrating neutrophils at different intratumoral subsites and in different molecular subgroups of CRC. The relations between neutrophil infiltration and infiltration of other immune cells (T-cell and macrophage subsets) were also addressed. Expression of the neutrophil marker CD66b was assessed by immunohistochemistry in 448 archival human tumor tissue samples from patients surgically resected for CRC. The infiltration of CD66b-positive cells was semi-quantitatively evaluated along the tumor invasive front, in the tumor center, and within the tumor epithelium (intraepithelial expression). We found that poor infiltration of CD66b-positive cells in the tumor front indicated a worse patient prognosis. The prognostic significance of CD66b infiltration was found to be mainly independent of tumor molecular characteristics and maintained significance in multivariable analysis of stage I-II colon cancers. We further analyzed the prognostic impact of CD66b-positive cells in relation to other immune markers (NOS2, CD163, Tbet, FOXP3, and CD8) and found that neutrophil infiltration, even though strongly correlated to infiltration of other immune cell subsets, had additional prognostic value. In conclusion, we find that low infiltration of neutrophils in the tumor front is an independent prognostic factor for a poorer patient prognosis in early stages of colon cancers. Further studies are needed to elucidate the biological role of neutrophils in colorectal carcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Single nucleotide polymorphisms in long noncoding RNA, ANRIL, are not associated with severe periodontitis but with adverse cardiovascular events among patients with cardiovascular disease.

PubMed

Schulz, S; Seitter, L; Werdan, K; Hofmann, B; Schaller, H-G; Schlitt, A; Reichert, S

2018-05-06

Biological plausibility of an association between severe periodontitis and cardiovascular disease (CVD) has been proven. Genetic characteristics play an important role in both complex inflammatory diseases. Polymorphisms (single nucleotide polymorphisms [SNPs]) in the long noncoding RNA, antisense noncoding RNA in the INK4 locus (ANRIL), were shown to play a leading role in both diseases. The primary objectives of the study were to assess, among cardiovascular (CV angiographically proven ≥50% stenosis of a main coronary artery) patients, the impact of ANRIL SNPs rs133049 and rs3217992 on the severity of periodontitis and the previous history of coronary events, as well as on the occurrence of further adverse CV events. The prevalence of severe periodontitis was analyzed in 1002 CV patients. ANRIL SNPs rs133049 and rs3217992 were genotyped. The prognostic value of both ANRIL SNPs for combined CV endpoint (stroke/transient ischemic attack [TIA], myocardial infarction, death from a CV-related event, death from stroke) was evaluated after a 3-year follow-up period. Hazard ratios (HRs) were adjusted for established CV risk factors applying Cox regression. ANRIL SNPs rs133049 and rs3217992 were not associated with severe periodontitis or history of CVD in CV patients. In the Kaplan-Meier survival curve including the log rank-test (P = .036) and Cox regression (hazard ratio = 1.684, P = .009) the AA genotype of rs3217992 was shown to be an independent predictor for adverse CV events after 3 years of follow-up. SNPs in ANRIL are not risk modulators for severe periodontitis and history of CVD in CV patients. The AA genotype of ANRIL SNPs rs3217992 possesses prognostic power for further CV events within 3 years of follow-up. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multicollinearity in prognostic factor analyses using the EORTC QLQ-C30: identification and impact on model selection.

PubMed

Van Steen, Kristel; Curran, Desmond; Kramer, Jocelyn; Molenberghs, Geert; Van Vreckem, Ann; Bottomley, Andrew; Sylvester, Richard

2002-12-30

Clinical and quality of life (QL) variables from an EORTC clinical trial of first line chemotherapy in advanced breast cancer were used in a prognostic factor analysis of survival and response to chemotherapy. For response, different final multivariate models were obtained from forward and backward selection methods, suggesting a disconcerting instability. Quality of life was measured using the EORTC QLQ-C30 questionnaire completed by patients. Subscales on the questionnaire are known to be highly correlated, and therefore it was hypothesized that multicollinearity contributed to model instability. A correlation matrix indicated that global QL was highly correlated with 7 out of 11 variables. In a first attempt to explore multicollinearity, we used global QL as dependent variable in a regression model with other QL subscales as predictors. Afterwards, standard diagnostic tests for multicollinearity were performed. An exploratory principal components analysis and factor analysis of the QL subscales identified at most three important components and indicated that inclusion of global QL made minimal difference to the loadings on each component, suggesting that it is redundant in the model. In a second approach, we advocate a bootstrap technique to assess the stability of the models. Based on these analyses and since global QL exacerbates problems of multicollinearity, we therefore recommend that global QL be excluded from prognostic factor analyses using the QLQ-C30. The prognostic factor analysis was rerun without global QL in the model, and selected the same significant prognostic factors as before. Copyright 2002 John Wiley & Sons, Ltd.

IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication.

PubMed

Paschka, Peter; Schlenk, Richard F; Gaidzik, Verena I; Habdank, Marianne; Krönke, Jan; Bullinger, Lars; Späth, Daniela; Kayser, Sabine; Zucknick, Manuela; Götze, Katharina; Horst, Heinz-A; Germing, Ulrich; Döhner, Hartmut; Döhner, Konstanze

2010-08-01

To analyze the frequency and prognostic impact of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations in acute myeloid leukemia (AML). We studied 805 adults (age range, 16 to 60 years) with AML enrolled on German-Austrian AML Study Group (AMLSG) treatment trials AML HD98A and APL HD95 for mutations in exon 4 of IDH1 and IDH2. Patients were also studied for NPM1, FLT3, MLL, and CEBPA mutations. The median follow-up for survival was 6.3 years. IDH mutations were found in 129 patients (16.0%) -IDH1 in 61 patients (7.6%), and IDH2 in 70 patients (8.7%). Two patients had both IDH1 and IDH2 mutations. All but one IDH1 mutation caused substitutions of residue R132; IDH2 mutations caused changes of R140 (n = 48) or R172 (n = 22). IDH mutations were associated with older age (P < .001; effect conferred by IDH2 only); lower WBC (P = .04); higher platelets (P < .001); cytogenetically normal (CN) -AML (P< .001); and NPM1 mutations, in particular with the genotype of mutated NPM1 without FLT3 internal tandem duplication (ITD; P < .001). In patients with CN-AML with the latter genotype, IDH mutations adversely impacted relapse-free survival (RFS; P = .02) and overall survival (P = .03), whereas outcome was not affected in patients with CN-AML who lacked this genotype. In CN-AML, multivariable analyses revealed a significant interaction between IDH mutation and the genotype of mutated NPM1 without FLT3-ITD (ie, the adverse impact of IDH mutation [RFS]; P = .046 was restricted to this patient subset). IDH1 and IDH2 mutations are recurring genetic changes in AML. They constitute a poor prognostic factor in CN-AML with mutated NPM1 without FLT3-ITD, which allows refined risk stratification of this AML subset.

Adverse environments and children's creativity development: transforming the notion of "success in adversity" in China.

PubMed

Cheng, Li; Tan, Mei; Liu, Zhengkui

2015-01-01

China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications for China's future as it brings together one of China's core cultural values-"success in adversity"-the importance of creativity, and very real social and economic needs. "Success in adversity" reflects the strongly held belief that individuals who suffer adverse environments can rise to excellence and success through persistence, effort, and creativity. In this article, we briefly explore the historical sources of this belief and how it is closely related to the Chinese conception of creativity. We then present some studies on the creativity of some of China's migrant children. Findings show that while migrant children as a group may not generally exhibit higher creativity than their urban peers as hypothesized, indications of resilience and creative potential suggest that the notion of success in adversity may contribute to the positive development of China's migrant children more substantially when it is informed by research and augmented by research-supported policy. © 2015 Wiley Periodicals, Inc.

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study

PubMed Central

Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei

2017-01-01

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log(des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment. PMID:28458303

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study.

PubMed

Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei

2017-01-01

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log (des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.

Circulating FABP4 is a prognostic biomarker in patients with acute coronary syndrome but not in asymptomatic individuals.

PubMed

Reiser, Hans; Klingenberg, Roland; Hof, Danielle; Cooksley-Decasper, Seraina; Fuchs, Nina; Akhmedov, Alexander; Zoller, Stefan; Marques-Vidal, Pedro; Marti Soler, Helena; Heg, Dik; Landmesser, Ulf; Rodondi, Nicolas; Mach, Francois; Windecker, Stephan; Vollenweider, Peter; Matter, Christian M; Lüscher, Thomas F; von Eckardstein, Arnold; Gawinecka, Joanna

2015-08-01

Blood-borne biomarkers reflecting atherosclerotic plaque burden have great potential to improve clinical management of atherosclerotic coronary artery disease and acute coronary syndrome (ACS). Using data integration from gene expression profiling of coronary thrombi versus peripheral blood mononuclear cells and proteomic analysis of atherosclerotic plaque-derived secretomes versus healthy tissue secretomes, we identified fatty acid-binding protein 4 (FABP4) as a biomarker candidate for coronary artery disease. Its diagnostic and prognostic performance was validated in 3 different clinical settings: (1) in a cross-sectional cohort of patients with stable coronary artery disease, ACS, and healthy individuals (n=820), (2) in a nested case-control cohort of patients with ACS with 30-day follow-up (n=200), and (3) in a population-based nested case-control cohort of asymptomatic individuals with 5-year follow-up (n=414). Circulating FABP4 was marginally higher in patients with ST-segment-elevation myocardial infarction (24.9 ng/mL) compared with controls (23.4 ng/mL; P=0.01). However, elevated FABP4 was associated with adverse secondary cerebrovascular or cardiovascular events during 30-day follow-up after index ACS, independent of age, sex, renal function, and body mass index (odds ratio, 1.7; 95% confidence interval, 1.1-2.5; P=0.02). Circulating FABP4 predicted adverse events with similar prognostic performance as the GRACE in-hospital risk score or N-terminal pro-brain natriuretic peptide. Finally, no significant difference between baseline FABP4 was found in asymptomatic individuals with or without coronary events during 5-year follow-up. Circulating FABP4 may prove useful as a prognostic biomarker in risk stratification of patients with ACS. © 2015 American Heart Association, Inc.

The association of chronic adversity with psychiatric disorder and disorder severity in adolescents.

PubMed

Benjet, Corina; Borges, Guilherme; Méndez, Enrique; Fleiz, Clara; Medina-Mora, Maria Elena

2011-09-01

The purpose of this paper is to estimate the impact of chronic adversity on psychopathology in adolescents, taking into account the type of adversity, number of adversities experienced and type of psychiatric disorder, as well as to estimate the impact on severity of the disorder. A total of 3,005 male and female adolescents from the Mexican Adolescent Mental Health Survey aged 12-17 years were interviewed in a stratified multistage general population probability survey. Assessment of 20 DSM-IV disorders, disorder severity and 12 chronic childhood adversities were assessed with the adolescent version of the World Mental Health Composite International Diagnostic Interview (WMH-CIDI-A). Family dysfunction adversities including abuse presented the most consistent associations between chronic adversity and psychopathology and their impact was generally non-specific with regard to the type of disorder. Parental divorce, parental death and economic adversity were not individually associated with psychopathology. Among those with a psychiatric disorder, sexual abuse and family violence were associated with having a seriously impairing disorder. The odds of having a psychiatric disorder and a serious disorder increased with increasing numbers of adversities; however, each additional adversity increased the odds at a decreasing rate. While the study design does not allow for conclusions regarding causality, these findings suggest general pathways from family dysfunction to psychopathology rather than specific associations between particular adversities and particular disorders, and provide further evidence for the importance of family-focused intervention and prevention efforts.

The impact of childhood adversity on suicidality and clinical course in treatment-resistant depression.

PubMed

Tunnard, Catherine; Rane, Lena J; Wooderson, Sarah C; Markopoulou, Kalypso; Poon, Lucia; Fekadu, Abebaw; Juruena, Mario; Cleare, Anthony J

2014-01-01

Childhood adversity is a risk factor for the development of depression and can also affect clinical course. We investigated this specifically in treatment-resistant depression (TRD). One hundred and thirty-seven patients with TRD previously admitted to an inpatient affective disorders unit were included. Clinical, demographic and childhood adversity (physical, sexual, emotional abuse; bullying victimization, traumatic events) data were obtained during admission. Associations between childhood adversity, depressive symptoms and clinical course were investigated. Most patients had experienced childhood adversity (62%), with traumatic events (35%) and bullying victimization (29%) most commonly reported. Childhood adversity was associated with poorer clinical course, including earlier age of onset, episode persistence and recurrence. Logistic regression analyses revealed childhood adversity predicted lifetime suicide attempts (OR 2.79; 95% CI 1.14, 6.84) and childhood physical abuse predicted lifetime psychosis (OR 3.42; 95% CI 1.00, 11.70). The cross-sectional design and retrospective measurement of childhood adversity are limitations of the study. Childhood adversity was common amongst these TRD patients and was associated with poor clinical course, psychosis and suicide attempts. Routine assessment of early adversity may help identify at risk individuals and inform clinical intervention. Copyright © 2013 Elsevier B.V. All rights reserved.

Distributed Prognostics based on Structural Model Decomposition

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, I.

2014-01-01

Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based models are constructed that describe the operation of a system and how it fails. Such approaches consist of an estimation phase, in which the health state of the system is first identified, and a prediction phase, in which the health state is projected forward in time to determine the end of life. Centralized solutions to these problems are often computationally expensive, do not scale well as the size of the system grows, and introduce a single point of failure. In this paper, we propose a novel distributed model-based prognostics scheme that formally describes how to decompose both the estimation and prediction problems into independent local subproblems whose solutions may be easily composed into a global solution. The decomposition of the prognostics problem is achieved through structural decomposition of the underlying models. The decomposition algorithm creates from the global system model a set of local submodels suitable for prognostics. Independent local estimation and prediction problems are formed based on these local submodels, resulting in a scalable distributed prognostics approach that allows the local subproblems to be solved in parallel, thus offering increases in computational efficiency. Using a centrifugal pump as a case study, we perform a number of simulation-based experiments to demonstrate the distributed approach, compare the performance with a centralized approach, and establish its scalability. Index Terms-model-based prognostics, distributed prognostics, structural model decomposition ABBREVIATIONS

The impact of adverse child and adult experiences on recovery from serious mental illness.

PubMed

Stumbo, Scott P; Yarborough, Bobbi Jo H; Paulson, Robert I; Green, Carla A

2015-12-01

The purpose of this study was to compare effects of adverse childhood experiences and adverse adult experiences on recovery from serious mental illnesses. As part of a mixed-methods study of recovery from serious mental illnesses, we interviewed and administered questionnaires to 177 members of a not-for-profit health plan over a 2-year period. Participants had a diagnosis of bipolar disorder, affective psychosis, schizophrenia, or schizoaffective disorder. Data for analyses came from standardized self-reported measures; outcomes included recovery, functioning, quality of life, and psychiatric symptoms. Adverse events in childhood and adulthood were evaluated as predictors. Child and adult exposures to adverse experiences were high, at 91% and 82%, respectively. Cumulative lifetime exposure to adverse experiences (childhood plus adult experiences) was 94%. In linear regression analyses, adverse adult experiences were more important predictors of outcomes than adverse childhood experiences. Adult experiences were associated with lower recovery scores, quality of life, mental and physical functioning and social functioning and greater psychiatric symptoms. Emotional neglect in adulthood was associated with lower recovery scores. Early and repeated exposure to adverse events was common in this sample of people with serious mental illnesses. Adverse adult experiences were stronger predictors of worse functioning and lower recovery levels than were childhood experiences. Focusing clinical attention on adult experiences of adverse or traumatic events may result in greater benefit than focusing on childhood experiences alone. (c) 2015 APA, all rights reserved).

The Impact of Adverse Child and Adult Experiences on Recovery from Serious Mental Illness

PubMed Central

Stumbo, Scott P.; Yarborough, Bobbi Jo H.; Paulson, Robert I.; Green, Carla A.

2015-01-01

Objective To compare effects of adverse childhood experiences and adverse adult experiences on recovery from serious mental illnesses. Methods As part of a mixed-methods study of recovery from serious mental illnesses, we interviewed and administered questionnaires to 177 members of a not-for-profit health plan over a two-year period. Participants had a diagnosis of bipolar disorder, affective psychosis, schizophrenia or schizoaffective disorder. Data for analyses came from standardized self-reported measures; outcomes included recovery, functioning, quality of life, and psychiatric symptoms. Adverse events in childhood and adulthood were evaluated as predictors. Results Child and adult exposures to adverse experiences were high, at 91% and 82% respectively. Cumulative lifetime exposure to adverse experiences (childhood plus adult experiences) was 94%. In linear regression analyses, adverse adult experiences were more important predictors of outcomes than adverse childhood experiences. Adult experiences were associated with lower recovery scores, quality of life, mental and physical functioning, social functioning, and greater psychiatric symptoms. Emotional neglect in adulthood was associated with lower recovery scores. Conclusions and Implications for Practice Early and repeated exposure to adverse events was common in this sample of people with serious mental illnesses. Adverse adult experiences were stronger predictors of worse functioning and lower recovery levels than were childhood experiences. Focusing clinical attention on adult experiences of adverse or traumatic events may result in greater benefit than focusing on childhood experiences alone. PMID:26053533

Prevalence and Impact of Co-morbidity Burden as Defined by the Charlson Co-morbidity Index on 30-Day and 1- and 5-Year Outcomes After Coronary Stent Implantation (from the Nobori-2 Study).

PubMed

Mamas, Mamas A; Fath-Ordoubadi, Farzin; Danzi, Gian B; Spaepen, Erik; Kwok, Chun Shing; Buchan, Iain; Peek, Niels; de Belder, Mark A; Ludman, Peter F; Paunovic, Dragica; Urban, Philip

2015-08-01

Co-morbidities have typically been considered as prevalent cardiovascular risk factors and cardiovascular diseases rather than systematic measures of general co-morbidity burden in patients who underwent percutaneous coronary intervention (PCI). Charlson co-morbidity index (CCI) is a measure of co-morbidity burden providing a means of quantifying the prognostic impact of 22 co-morbid conditions on the basis of their number and prognostic impact. The study evaluated the impact of the CCI on cardiac mortality and major adverse cardiovascular events (MACE) after PCI through analysis of the Nobori-2 study. The prognostic impact of CCI was studied in 3,067 patients who underwent PCI in 4,479 lesions across 125 centers worldwide on 30-day and 1- and 5-year cardiac mortality and MACE. Data were adjusted for potential confounders using stepwise logistic regression; 2,280 of 3,067 patients (74.4%) had ≥1 co-morbid conditions. CCI (per unit increase) was independently associated with an increase in both cardiac death (odds ratio [OR] 1.47 95% confidence interval [CI] 1.20 to 1.80, p = 0.0002) and MACE (OR 1.29 95% CI 1.14 to 1.47, p ≤0.0011) at 30 days, with similar observations recorded at 1 and 5 years. CCI score ≥2 was independently associated with increased 30-day cardiac death (OR 4.25, 95% CI 1.24 to 14.56, p = 0.02) at 1 month, and this increased risk was also observed at 1 and 5 years. In conclusion, co-morbid burden, as measured using CCI, is an independent predictor of adverse outcomes in the short, medium, and long term. Co-morbidity should be considered in the decision-making process when counseling patients regarding the periprocedural risks associated with PCI, in conjunction with traditional risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Prognostic Value of Coronary Computed Tomography Imaging in Patients at High Risk Without Symptoms of Coronary Artery Disease.

PubMed

Dedic, Admir; Ten Kate, Gert-Jan R; Roos, Cornelis J; Neefjes, Lisan A; de Graaf, Michiel A; Spronk, Angela; Delgado, Victoria; van Lennep, Jeanine E Roeters; Moelker, Adriaan; Ouhlous, Mohamed; Scholte, Arthur J H A; Boersma, Eric; Sijbrands, Eric J G; Nieman, Koen; Bax, Jeroen J; de Feijter, Pim J

2016-03-01

At present, traditional risk factors are used to guide cardiovascular management of asymptomatic subjects. Intensified surveillance may be warranted in those identified as high risk of developing cardiovascular disease (CVD). This study aims to determine the prognostic value of coronary computed tomography (CT) angiography (CCTA) next to the coronary artery calcium score (CACS) in patients at high CVD risk without symptoms suspect for coronary artery disease (CAD). A total of 665 patients at high risk (mean age 56 ± 9 years, 417 men), having at least one important CVD risk factor (diabetes mellitus, familial hypercholesterolemia, peripheral artery disease, or severe hypertension) or a calculated European systematic coronary risk evaluation of >10% were included from outpatient clinics at 2 academic centers. Follow-up was performed for the occurrence of adverse events including all-cause mortality, nonfatal myocardial infarction, unstable angina, or coronary revascularization. During a median follow-up of 3.0 (interquartile range 1.3 to 4.1) years, adverse events occurred in 40 subjects (6.0%). By multivariate analysis, adjusted for age, gender, and CACS, obstructive CAD on CCTA (≥50% luminal stenosis) was a significant predictor of adverse events (hazard ratio 5.9 [CI 1.3 to 26.1]). Addition of CCTA to age, gender, plus CACS, increased the C statistic from 0.81 to 0.84 and resulted in a total net reclassification index of 0.19 (p <0.01). In conclusion, CCTA has incremental prognostic value and risk reclassification benefit beyond CACS in patients without CAD symptoms but with high risk of developing CVD. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of air pollution and temperature on adverse birth outcomes: Madrid, 2001-2009.

PubMed

Arroyo, Virginia; Díaz, Julio; Carmona, Rocío; Ortiz, Cristina; Linares, Cristina

2016-11-01

Low birth weight (<2500 g) (LBW), premature birth (<37 weeks of gestation) (PB), and late foetal death (<24 h of life) (LFD) are causes of perinatal morbi-mortality, with short- and long-term social and economic health impacts. This study sought to identify gestational windows of susceptibility during pregnancy and to analyse and quantify the impact of different air pollutants, noise and temperature on the adverse birth outcomes. Time-series study to assess the impact of mean daily PM 2.5 , NO 2 and O 3 (μg/m 3 ), mean daily diurnal (Leqd) and nocturnal (Leqn) noise levels (dB(A)), maximum and minimum daily temperatures (°C) on the number of births with LBW, PB or LFD in Madrid across the period 2001-2009. We controlled for linear trend, seasonality and autoregression. Poisson regression models were fitted for quantification of the results. The final models were expressed as relative risk (RR) and population attributable risk (PAR). Leqd was observed to have the following impacts in LBW: at onset of gestation, in the second trimester and in the week of birth itself. NO 2 had an impact in the second trimester. In the case of PB, the following: Leqd in the second trimester, Leqn in the week before birth and PM 2.5 in the second trimester. In the case of LFD, impacts were observed for both PM 2.5 in the third trimester, and minimum temperature. O 3 proved significant in the first trimester for LBW and PB, and in the second trimester for LFD. Pollutants concentrations, noise and temperature influenced the weekly average of new-borns with LBW, PB and LFD in Madrid. Special note should be taken of the effect of diurnal noise on LBW across the entire pregnancy. The exposure of pregnant population to the environmental factors analysed should therefore be controlled with a view to reducing perinatal morbi-mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prognostic significance of surgical extranodal extension in head and neck squamous cell carcinoma patients.

PubMed

Matsumoto, Fumihiko; Mori, Taisuke; Matsumura, Satoko; Matsumoto, Yoshifumi; Fukasawa, Masahiko; Teshima, Masanori; Kobayashi, Kenya; Yoshimoto, Seiichi

2017-08-01

Lymph node metastasis with extranodal extension represents one of the most important adverse prognostic factors for survival in patients with head and neck squamous cell carcinoma. We propose that extranodal extension occurs to differing extents. The aim of this study was to determine the prognostic significance of extranodal extension in patients with head and neck squamous cell carcinoma. Two hundred and ninety-eight patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection were included. Cervical lymph nodes were classified into four categories: (i) pathological N negative, (ii) extranodal extension negative, (iii) non-surgical extranodal extension and (iv) surgical extranodal extension. Lymph node metastases were detected in 67.1% of laryngeal/hypopharyngeal cancer patients and 52.7% of oral cancer patients. The 3-year disease-specific survival rates for patients in the pathological N negative, extranodal extension negative, non-surgical extranodal extension and surgical extranodal extension groups were 90.9%, 79.6%, 63.8% and 48.3%, respectively. In laryngeal/hypopharyngeal cancer patients, surgical extranodal extension was associated with a significantly poorer disease-specific survival than a pathological N negative, extranodal extension negative or non-surgical extranodal extension status. In oral cancer patients, no significant differences were observed between the non-surgical and surgical extranodal extension groups. However, non-surgical extranodal extension was associated with a poorer disease-specific survival than a pathological N negative or extranodal extension negative status. Surgical extranodal extension was a poor prognostic factor in patients with head and neck squamous cell carcinoma. The prognostic significance of surgical extranodal extension differed between laryngeal/hypopharyngeal and oral cancer patients. The clinical significance of surgical extranodal extension was much greater for

Value of the prognostic nutritional index in advanced gastric cancer treated with preoperative chemotherapy.

PubMed

Sun, Jianyi; Wang, Donghai; Mei, Ying; Jin, Hailong; Zhu, Kankai; Liu, Xiaosun; Zhang, Qing; Yu, Jiren

2017-03-01

The prognostic nutritional index (PNI) is a useful parameter indicating the immune and nutritional status of cancer patients; this study investigated the prognostic value of the PNI in advanced gastric cancer patients treated with preoperative chemotherapy. We retrospectively reviewed 117 advanced gastric cancer patients who met the inclusion criteria for preoperative chemotherapy and underwent surgical resection from July 2004 to December 2011. The patients were divided into PNI-high (PNI ≥ 45) and PNI-low (PNI < 45) groups. Clinicopathologic features, chemotherapy adverse events, and surgical complications were compared between the prechemotherapy PNI-high and PNI-low groups using the chi-square test. Survival analysis was performed using the Kaplan-Meier method and log-rank test. The Cox proportional hazard model was used to identify prognostic factors. Overall survival was better in the prechemotherapy PNI-high group than in the PNI-low group (hazard ratio [HR] = 2.237, 95% confidence interval [CI]: 1.271-3.393, P = 0.005), while there was no significant difference in Overall survival between the postchemotherapy PNI-high and PNI-low groups (P > 0.05). Cox regression analysis indicated that yield pathologic T (ypT), yield pathologic N (ypN) stage, and prechemotherapy PNI were independent prognostic factors (ypT: HR = 2.914, 95% CI = 1.312-6.470, P = 0.009; ypN: HR = 4.909, 95% CI = 1.764-13.660, P = 0.003; prechemotherapy PNI: HR = 1.963, 95% CI = 1.101-3.499, P = 0.022). The prechemotherapy PNI is a useful predictor of the long-term outcome of patients with advanced gastric cancer treated with preoperative chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic role of ABO blood type in patients with extranodal natural killer/T cell lymphoma, nasal type: a triple-center study.

PubMed

Li, Ya-Jun; Yi, Ping-Yong; Li, Ji-Wei; Liu, Xian-Ling; Tang, Tian; Zhang, Pei-Ying; Jiang, Wen-Qi

2017-07-31

The prognostic significance of ABO blood type for lymphoma is largely unknown. We evaluated the prognostic role of ABO blood type in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed clinical data of 697 patients with newly diagnosed ENKTL from three cancer centers. The prognostic value of ABO blood type was evaluated using Kaplan-Meier curves and Cox proportional hazard models. The prognostic values of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were also evaluated. Compared with patients with blood type O, those with blood type non-O tended to display elevated baseline serum C-reactive protein levels (P = 0.038), lower rate of complete remission (P = 0.005), shorter progression-free survival (PFS, P < 0.001), and shorter overall survival (OS, P = 0.001). Patients with blood type O/AB had longer PFS (P < 0.001) and OS (P = 0.001) compared with those with blood type A/B. Multivariate analysis demonstrated that age >60 years (P < 0.001), mass ≥5 cm (P = 0.001), stage III/IV (P < 0.001), elevated serum lactate dehydrogenase (LDH) levels (P = 0.001), and blood type non-O were independent adverse predictors of OS (P = 0.001). ABO blood type was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the intermediate-to-low- and high-to-intermediate-risk groups. ABO blood type was an independent predictor of clinical outcome for patients with ENKTL.

Identification and Prioritization of Relationships between Environmental Stressors and Adverse Human Health Impacts.

PubMed

Bell, Shannon M; Edwards, Stephen W

2015-11-01

There are > 80,000 chemicals in commerce with few data available describing their impacts on human health. Biomonitoring surveys, such as the NHANES (National Health and Nutrition Examination Survey), offer one route to identifying possible relationships between environmental chemicals and health impacts, but sparse data and the complexity of traditional models make it difficult to leverage effectively. We describe a workflow to efficiently and comprehensively evaluate and prioritize chemical-health impact relationships from the NHANES biomonitoring survey studies. Using a frequent itemset mining (FIM) approach, we identified relationships between chemicals and health biomarkers and diseases. The FIM method identified 7,848 relationships between 219 chemicals and 93 health outcomes/biomarkers. Two case studies used to evaluate the FIM rankings demonstrate that the FIM approach is able to identify published relationships. Because the relationships are derived from the vast majority of the chemicals monitored by NHANES, the resulting list of associations is appropriate for evaluating results from targeted data mining or identifying novel candidate relationships for more detailed investigation. Because of the computational efficiency of the FIM method, all chemicals and health effects can be considered in a single analysis. The resulting list provides a comprehensive summary of the chemical/health co-occurrences from NHANES that are higher than expected by chance. This information enables ranking and prioritization on chemicals or health effects of interest for evaluation of published results and design of future studies. Bell SM, Edwards SW. 2015. Identification and prioritization of relationships between environmental stressors and adverse human health impacts. Environ Health Perspect 123:1193-1199; http://dx.doi.org/10.1289/ehp.1409138.

Impact of Adverse Events Following Immunization in Viet Nam in 2013 on chronic hepatitis B infection.

PubMed

Li, Xi; Wiesen, Eric; Diorditsa, Sergey; Toda, Kohei; Duong, Thi Hong; Nguyen, Lien Huong; Nguyen, Van Cuong; Nguyen, Tran Hien

2016-02-03

Adverse Events Following Immunization in Viet Nam in 2013 led to substantial reductions in hepatitis B vaccination coverage (both the birth dose and the three-dose series). In order to estimate the impact of the reduction in vaccination coverage on hepatitis B transmission and future mortality, a widely-used mathematical model was applied to the data from Viet Nam. Using the model, we estimated the number of chronic infections and deaths that are expected to occur in the birth cohort in 2013 and the number of excessive infections and deaths attributable to the drop in immunization coverage in 2013. An excess of 90,137 chronic infections and 17,456 future deaths were estimated to occur in the 2013 birth cohort due to the drop in vaccination coverage. This analysis highlights the importance of maintaining high vaccination coverage and swiftly responding to reported Adverse Events Following Immunization in order to regain consumer confidence in the hepatitis B vaccine. Copyright © 2015 World Health Organization; licensee Elsevier. Published by Elsevier Ltd.. All rights reserved.

Fasting blood glucose is a novel prognostic indicator for extranodal natural killer/T-cell lymphoma, nasal type

PubMed Central

Cai, Q; Luo, X; Liang, Y; Rao, H; Fang, X; Jiang, W; Lin, T; Lin, T; Huang, H

2013-01-01

Background: Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease with poor prognosis, requiring risk stratification. However, the prognosis of ENKTL is not fully defined and needs supplementation. We hypothesised that fasting blood glucose (FBG) may be a new prognostic factor for ENKTL. Methods: We retrospectively analysed 130 patients newly diagnosed with ENKTL. Results: Both univariate analysis and multivariate analysis revealed that FBG >100 mg dl−1 was associated with a poor outcome. Patients with FBG >100 mg dl−1 at diagnosis had more adverse clinical features, achieved lower complete remission rates (P=0.003) and had worse overall survival (P<0.001) and progression-free survival (P<0.001) compared with low-FBG patients. Measurement of FBG was helpful in differentiating between low-risk patients using the International Prognostic Index (IPI) and Prognosis Index for peripheral T-cell lymphoma (PIT) scoring and patients in a different category using the Korean Prognostic Index (KPI) scores with different survival outcomes (P<0.05). Conclusion: Our data suggest that measuring FBG levels at diagnosis is a novel, independent predictor of prognosis in ENKTL and helps to distinguish low-risk patients with poor survival, and this holds true in patients considered low-risk by IPI, PIT and KPI. PMID:23299534

Prognostic factors of phyllodes tumor of the breast.

PubMed

Roa, Juan Carlos; Tapia, Oscar; Carrasco, Paula; Contreras, Enrique; Araya, Juan Carlos; Muñoz, Sergio; Roa, Iván

2006-06-01

The phyllodes tumor is characterized by its tendency to recur locally and occasionally to metastasize. The purpose of the present paper was to assess the prognostic value of clinical-morphological characteristics in patients with phyllodes tumor. Forty-seven cases of phyllodes tumors was studied; the World Health Organization classification was used and follow up was obtained. A total of 51%, 28% and 21% of the tumors were classified as benign, borderline and malignant, respectively. The adherence (P = 0.01), size >10 cm (P = 0.001), high mitotic activity (P = 0.03), infiltrative tumor margin (P = 0.0002) and type of surgery in malignant tumors (P = 0.02) proved to be good predictors of relapse. The presence of pain (P = 0.03), postmenopausal status (P < 0.04), heavy cellular pleomorphism (P = 0.007), high mitotic activity (P = 0.002), tumoral grade (P = 0.006) and metastasis (P < 0.00001) were prognostic factors of poor survival. Tumoral grade and some clinical-morphological characteristics of patients with phyllodes tumors have a significant impact on the prediction of its biological behavior.

A new extranodal scoring system based on the prognostically relevant extranodal sites in diffuse large B-cell lymphoma, not otherwise specified treated with chemoimmunotherapy.

PubMed

Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

2016-08-01

Extranodal involvement is a well-known prognostic factor in patients with diffuse large B-cell lymphomas (DLBCL). Nevertheless, the prognostic impact of the extranodal scoring system included in the conventional international prognostic index (IPI) has been questioned in an era where rituximab treatment has become widespread. We investigated the prognostic impacts of individual sites of extranodal involvement in 761 patients with DLBCL who received rituximab-based chemoimmunotherapy. Subsequently, we established a new extranodal scoring system based on extranodal sites, showing significant prognostic correlation, and compared this system with conventional scoring systems, such as the IPI and the National Comprehensive Cancer Network-IPI (NCCN-IPI). An internal validation procedure, using bootstrapped samples, was also performed for both univariate and multivariate models. Using multivariate analysis with a backward variable selection, we found nine extranodal sites (the liver, lung, spleen, central nervous system, bone marrow, kidney, skin, adrenal glands, and peritoneum) that remained significant for use in the final model. Our newly established extranodal scoring system, based on these sites, was better correlated with patient survival than standard scoring systems, such as the IPI and the NCCN-IPI. Internal validation by bootstrapping demonstrated an improvement in model performance of our modified extranodal scoring system. Our new extranodal scoring system, based on the prognostically relevant sites, may improve the performance of conventional prognostic models of DLBCL in the rituximab era and warrants further external validation using large study populations.

Quality of life in children with adverse drug reactions: a narrative and systematic review.

PubMed

Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

2015-10-01

Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn's disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. © 2014 The British Pharmacological Society.

Quality of life in children with adverse drug reactions: a narrative and systematic review

PubMed Central

Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

2015-01-01

Aims Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. Methods We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Results Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn’s disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. Conclusions To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. PMID:24833305

Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twu, C.-W.; Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung; Wang, W.-Y.

Purpose: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. Methods and Materials: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. Results: Relapsedmore » patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. Conclusion: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.« less

HOXB2, an adverse prognostic indicator for stage I lung adenocarcinomas, promotes invasion by transcriptional regulation of metastasis-related genes in HOP-62 non-small cell lung cancer cells.

PubMed

Inamura, Kentaro; Togashi, Yuki; Ninomiya, Hironori; Shimoji, Takashi; Noda, Tetsuo; Ishikawa, Yuichi

2008-01-01

Previously, using microarray and real-time RT-PCR analysis, we established that HOXB2 is an adverse prognostic indicator for Stage I lung adenocarcinomas. HOXB2 is one of the homeobox master development-controlling genes regulating morphogenesis and cell differentiation. The molecular functions of HOXB2 were analyzed with a small interfering RNA (siRNA) approach in HOP-62 human non-small cell lung cancer (NSCLC) cells featuring high HOXB2 expression. Matrigel invasion assays and microarray gene expression analysis were compared between the HOXB2-siRNA cells and the control cells. The Matrigel invasion assays showed attenuation of HOXB2 expression by siRNA to result in a significant decrease of invasiveness compared to the control cells (p = 0.0013, paired t-test). On microarray gene expression analysis, up-regulation of many metastasis-related genes and others correlating with HOXB2 expression was observed in the control case. With attenuation of HOXB2 expression, downregulation was noted for laminins alpha 4 and 5, involved in enriched signaling, and for Mac-2BP (Mac-2 binding protein) and integrin beta 4 amongst the genes having an enriched glycoprotein ontology. HOXB2 promotes invasion of lung cancer cells through the regulation of metastasis-related genes.

Adverse Environments and Children's Creativity Development: Transforming the Notion of "Success in Adversity" in China

ERIC Educational Resources Information Center

Cheng, Li; Tan, Mei; Liu, Zhengkui

2015-01-01

China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications…

Circulating Endothelial Cells and Endothelial Function predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction

PubMed Central

Magdy, Abdel Hamid; Bakhoum, Sameh; Sharaf, Yasser; Sabry, Dina; El-Gengehe, Ahmed T; Abdel-Latif, Ahmed

2016-01-01

Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+ CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major cardiac adverse events (MACE) consisting of all-cause mortality, recurrent non-fatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), vWF level (P =0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82 respectively for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (p =0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID:26864952

Pneumococcal pneumonia - Are the new severity scores more accurate in predicting adverse outcomes?

PubMed

Ribeiro, C; Ladeira, I; Gaio, A R; Brito, M C

2013-01-01

The site-of-care decision is one of the most important factors in the management of patients with community-acquired pneumonia. The severity scores are validated prognostic tools for community-acquired pneumonia mortality and treatment site decision. The aim of this paper was to compare the discriminatory power of four scores - the classic PSI and CURB65 ant the most recent SCAP and SMART-COP - in predicting major adverse events: death, ICU admission, need for invasive mechanical ventilation or vasopressor support in patients admitted with pneumococcal pneumonia. A five year retrospective study of patients admitted for pneumococcal pneumonia. Patients were stratified based on admission data and assigned to low-, intermediate-, and high-risk classes for each score. Results were obtained comparing low versus non-low risk classes. We studied 142 episodes of hospitalization with 2 deaths and 10 patients needing mechanical ventilation and vasopressor support. The majority of patients were classified as low risk by all scores - we found high negative predictive values for all adverse events studied, the most negative value corresponding to the SCAP score. The more recent scores showed better accuracy for predicting ICU admission and need for ventilation or vasopressor support (mostly for the SCAP score with higher AUC values for all adverse events). The rate of all adverse outcomes increased directly with increasing risk class in all scores. The new gravity scores appear to have a higher discriminatory power in all adverse events in our study, particularly, the SCAP score. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Impact of Adverse Childhood Experiences on Psychotic-Like Symptoms and Stress Reactivity in Daily Life in Nonclinical Young Adults

PubMed Central

Ballespí, Sergi; Mitjavila, Mercè; Myin-Germeys, Inez; Kwapil, Thomas R.; Barrantes-Vidal, Neus

2016-01-01

Background There is increasing interest in elucidating the association of different childhood adversities with psychosis-spectrum symptoms as well as the mechanistic processes involved. This study used experience sampling methodology to examine (i) associations of a range of childhood adversities with psychosis symptom domains in daily life; (ii) whether associations of abuse and neglect with symptoms are consistent across self-report and interview methods of trauma assessment; and (iii) the role of different adversities in moderating affective, psychotic-like, and paranoid reactivity to situational and social stressors. Method A total of 206 nonclinical young adults were administered self-report and interview measures to assess childhood abuse, neglect, bullying, losses, and general traumatic events. Participants received personal digital assistants that signaled them randomly eight times daily for one week to complete questionnaires about current experiences, including symptoms, affect, and stress. Results Self-reported and interview-based abuse and neglect were associated with psychotic-like and paranoid symptoms, whereas only self-reported neglect was associated with negative-like symptoms. Bullying was associated with psychotic-like symptoms. Losses and general traumatic events were not directly associated with any of the symptom domains. All the childhood adversities were associated with stress reactivity in daily life. Interpersonal adversities (abuse, neglect, bullying, and losses) moderated psychotic-like and/or paranoid reactivity to situational and social stressors, whereas general traumatic events moderated psychotic-like reactivity to situational stress. Also, different interpersonal adversities exacerbated psychotic-like and/or paranoid symptoms in response to distinct social stressors. Discussion The present study provides a unique examination of how childhood adversities impact the expression of spectrum symptoms in the real world and lends support

Serum amyloid A as a prognostic marker in melanoma identified by proteomic profiling.

PubMed

Findeisen, Peter; Zapatka, Marc; Peccerella, Teresa; Matzk, Heike; Neumaier, Michael; Schadendorf, Dirk; Ugurel, Selma

2009-05-01

Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers. Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays. MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients' progression-free and overall survival. SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment.

Prognostic categories and timing of negative prognostic communication from critical care physicians to family members at end-of-life in an intensive care unit.

PubMed

Gutierrez, Karen M

2013-09-01

Negative prognostic communication is often delayed in intensive care units, which limits time for families to prepare for end-of-life. This descriptive study, informed by ethnographic methods, was focused on exploring critical care physician communication of negative prognoses to families and identifying timing influences. Prognostic communication of critical care physicians to nurses and family members was observed and physicians and family members were interviewed. Physician perception of prognostic certainty, based on an accumulation of empirical data, and the perceived need for decision-making, drove the timing of prognostic communication, rather than family needs. Although prognoses were initially identified using intuitive knowledge for patients in one of the six identified prognostic categories, utilizing decision-making to drive prognostic communication resulted in delayed prognostic communication to families until end-of-life (EOL) decisions could be justified with empirical data. Providers will better meet the needs of families who desire earlier prognostic information by separating prognostic communication from decision-making and communicating the possibility of a poor prognosis based on intuitive knowledge, while acknowledging the uncertainty inherent in prognostication. This sets the stage for later prognostic discussions focused on EOL decisions, including limiting or withdrawing treatment, which can be timed when empirical data substantiate intuitive prognoses. This allows additional time for families to anticipate and prepare for end-of-life decision-making. © 2012 John Wiley & Sons Ltd.

Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

PubMed

Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

2016-12-01

Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD. © The European Society of Cardiology 2015.

Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the Children's Oncology Group.

PubMed

Pollack, Ian F; Hamilton, Ronald L; Burger, Peter C; Brat, Daniel J; Rosenblum, Marc K; Murdoch, Geoffrey H; Nikiforova, Marina N; Holmes, Emiko J; Zhou, Tianni; Cohen, Kenneth J; Jakacki, Regina I

2010-09-01

Aberrant activation of Akt is a common finding in adult malignant gliomas, resulting in most cases from mutations or deletions involving PTEN, which allows constitutive Akt phosphorylation. In contrast, we have previously reported that pediatric malignant gliomas, which are morphologically similar to lesions arising in adults, have a substantially lower incidence of genomic alterations of PTEN. The objective of this study was to determine whether Akt activation was also an uncommon finding in childhood malignant gliomas and whether this feature was associated with survival. To address this issue, we examined the frequency of Akt activation, determined by overexpression of the activated phosphorylated form of Akt (Se(473)) on immunohistochemical analysis, in a series of 53 childhood malignant gliomas obtained from newly diagnosed patients treated on the Children's Oncology Group ACNS0126 and 0423 studies. The relationship between Akt activation and p53 overexpression, MIB1 labeling, and tumor histology was evaluated. The association between Akt activation and survival was also assessed. Overexpression of activated Akt was observed in 42 of 53 tumors, far in excess of the frequency of PTEN mutations we have previously observed. There was no association between Akt activation and either histology, p53 overexpression, or MIB1 proliferation indices. Although tumors that lacked Akt overexpression had a trend toward more favorable event-free survival and overall survival (p = 0.06), this association reflected that non-overexpressing tumors were significantly more likely to have undergone extensive tumor removal, which was independently associated with outcome. Activation of Akt is a common finding in pediatric malignant gliomas, although it remains uncertain whether this is an independent adverse prognostic factor. In view of the frequency of Akt activation, the evaluation of molecularly targeted therapies that inhibit this pathway warrants consideration for these tumors.

The impact of endocrine supplementation on adverse events in septic shock.

PubMed

Bissell, Brittany D; Erdman, Michael J; Smotherman, Carmen; Kraemer, Dale F; Ferreira, Jason A

2015-12-01

The objective of this study was to compare the incidence of severe adverse events of vasopressin vs hydrocortisone for endocrine support therapy in patients with septic shock. This was a retrospective, propensity-matched cohort of patients admitted to the medical intensive care unit with septic shock between February 2012 and February 2015. Patients were included if vasopressin or hydrocortisone was administered for hemodynamic support secondary to norepinephrine. In the unmatched cohort of 124 patients, vasopressin was associated with a significant decrease in the number of severe adverse events (P=.03). In the matched cohort, severe adverse events occurred 3 times as often in patients receiving hydrocortisone; however, this difference was not statistically significant. (odds ratio, 3.33; 95% confidence interval, 0.92-12.11; P=.06). In the matched cohort, vasopressin was associated with a faster time to hemodynamic stability (P<.05) and discontinuation of hemodynamic support (P<.01) with an increased requirement for third-line therapy (P<.01). No statistical differences were seen in length of stay (intensive care unit and hospital), length of mechanical ventilation, and in-hospital mortality. Given the lower incidence of adverse events and faster time to hemodynamic stability, vasopressin appears to be the most advantageous endocrine agent for hemodynamic support in septic shock. Copyright © 2015 Elsevier Inc. All rights reserved.

Ventral striatal activity links adversity and reward processing in children.

PubMed

Kamkar, Niki H; Lewis, Daniel J; van den Bos, Wouter; Morton, J Bruce

2017-08-01

Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain's sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Acute renal failure requiring renal replacement therapy in the intensive care unit: impact on prognostic assessment for shared decision making.

PubMed

Johnson, Robert F; Gustin, Jillian

2011-07-01

A 69-year-old female was receiving renal replacement therapy (RRT) for acute renal failure (ARF) in an intensive care unit (ICU). Consultation was requested from the palliative medicine service to facilitate a shared decision-making process regarding goals of care. Clinician responsibility in shared decision making includes the formulation and expression of a prognostic assessment providing the necessary perspective for a spokesperson to match patient values with treatment options. For this patient, ARF requiring RRT in the ICU was used as a focal point for preparing a prognostic assessment. A prognostic assessment should include the outcomes of most importance to a discussion of goals of care: mortality risk and survivor functional status, in this case including renal recovery. A systematic review of the literature was conducted to document published data regarding these outcomes for adult patients receiving RRT for ARF in the ICU. Forty-one studies met the inclusion criteria. The combined mean values for short-term mortality, long-term mortality, renal-function recovery of short-term survivors, and renal-function recovery of long-term survivors were 51.7%, 68.6%, 82.0%, and 88.4%, respectively. This case example illustrates a process for formulating and expressing a prognostic assessment for an ICU patient requiring RRT for ARF. Data from the literature review provide baseline information that requires adjustment to reflect specific patient circumstances. The nature of the acute primary process, comorbidities, and severity of illness are key modifiers. Finally, the prognostic assessment is expressed during a family meeting using recommended principles of communication.

Metrics for Offline Evaluation of Prognostic Performance

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

2010-01-01

Prognostic performance evaluation has gained significant attention in the past few years. Currently, prognostics concepts lack standard definitions and suffer from ambiguous and inconsistent interpretations. This lack of standards is in part due to the varied end-user requirements for different applications, time scales, available information, domain dynamics, etc. to name a few. The research community has used a variety of metrics largely based on convenience and their respective requirements. Very little attention has been focused on establishing a standardized approach to compare different efforts. This paper presents several new evaluation metrics tailored for prognostics that were recently introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. These metrics have the capability of incorporating probabilistic uncertainty estimates from prognostic algorithms. In addition to quantitative assessment they also offer a comprehensive visual perspective that can be used in designing the prognostic system. Several methods are suggested to customize these metrics for different applications. Guidelines are provided to help choose one method over another based on distribution characteristics. Various issues faced by prognostics and its performance evaluation are discussed followed by a formal notational framework to help standardize subsequent developments.

Vehicle Integrated Prognostic Reasoner (VIPR) Metric Report

NASA Technical Reports Server (NTRS)

Cornhill, Dennis; Bharadwaj, Raj; Mylaraswamy, Dinkar

2013-01-01

This document outlines a set of metrics for evaluating the diagnostic and prognostic schemes developed for the Vehicle Integrated Prognostic Reasoner (VIPR), a system-level reasoner that encompasses the multiple levels of large, complex systems such as those for aircraft and spacecraft. VIPR health managers are organized hierarchically and operate together to derive diagnostic and prognostic inferences from symptoms and conditions reported by a set of diagnostic and prognostic monitors. For layered reasoners such as VIPR, the overall performance cannot be evaluated by metrics solely directed toward timely detection and accuracy of estimation of the faults in individual components. Among other factors, overall vehicle reasoner performance is governed by the effectiveness of the communication schemes between monitors and reasoners in the architecture, and the ability to propagate and fuse relevant information to make accurate, consistent, and timely predictions at different levels of the reasoner hierarchy. We outline an extended set of diagnostic and prognostics metrics that can be broadly categorized as evaluation measures for diagnostic coverage, prognostic coverage, accuracy of inferences, latency in making inferences, computational cost, and sensitivity to different fault and degradation conditions. We report metrics from Monte Carlo experiments using two variations of an aircraft reference model that supported both flat and hierarchical reasoning.

Prognostic Significance of Human Apurinic/Apyrimidinic Endonuclease (APE/Ref-1) Expression in Rectal Cancer Treated With Preoperative Radiochemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jun-Sang, E-mail: k423j@cnu.ac.kr; Cancer Research Institute, Chungnam National University, Daejeon; Kim, Jin-Man

adverse prognostic factor for LARC patients who receive preoperative radiochemotherapy.« less

Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas.

PubMed

Busch, Jonas; Ralla, Bernhard; Jung, Monika; Wotschofsky, Zofia; Trujillo-Arribas, Elena; Schwabe, Philipp; Kilic, Ergin; Fendler, Annika; Jung, Klaus

2015-06-14

Piwi-interacting RNAs (piRNAs) are small RNAs of 27-30 nucleotides mapping to transposons or clustering in repeat genomic regions. Preliminary studies suggest an important role in cancerogenesis. This study is the first one investigating their prognostic impact in clear cell renal cell cancer (ccRCC) patients. Three piRNAs (piR-30924, piR-57125, and piR-38756) selected on the basis of initial piRNA microarray analyses were determined using RT-qPCR in non-metastatic (n = 76) and metastatic (n = 30) ccRCC tissue at the time of nephrectomy in comparison to normal renal tissue (n = 77) and tissue from distant ccRCC metastases (n = 13). Primary clinical end points were recurrence-free and overall survival. piR-57125 showed lower expression in metastatic than in non-metastatic tumors, whereas the expression of piR-30924 and piR-38756 increased in metastatic tumors. The higher expression of piR-30924 and piR-38756 as well as the lower expression of piR-57125 in metastatic primary tumors were significantly associated with tumor recurrence and overall survival. Multivariate Cox regression analyses revealed both piR-30924 and piR-57125 as independent prognostic predictors. This impact was even more pronounced in non-metastatic patients. This study demonstrates that the expression levels of these piRNAs in primary non-metastatic and metastatic ccRCC tissue can serve as potential prognostic biomarkers in combination with clinicopathological factors.

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia

PubMed Central

Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stéphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystèle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hélène; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hélène; Leblondon, Véronique

2013-01-01

Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics. This trial is registered with Clinicaltrials.gov, numbers NCT00566332 and NCT00608374. PMID:23065509

Cytogenetic prognostication within medulloblastoma subgroups.

PubMed

Shih, David J H; Northcott, Paul A; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M; Garzia, Livia; Peacock, John; Mack, Stephen C; Wu, Xiaochong; Rolider, Adi; Morrissy, A Sorana; Cavalli, Florence M G; Jones, David T W; Zitterbart, Karel; Faria, Claudia C; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G; Liau, Linda M; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K; Thompson, Reid C; Bailey, Simon; Lindsey, Janet C; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M C; Scherer, Stephen W; Phillips, Joanna J; Gupta, Nalin; Fan, Xing; Muraszko, Karin M; Vibhakar, Rajeev; Eberhart, Charles G; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F; Weiss, William A; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R; Rubin, Joshua B; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M; Gajjar, Amar; Packer, Roger J; Rutkowski, Stefan; Pomeroy, Scott L; French, Pim J; Kloosterhof, Nanne K; Kros, Johan M; Van Meir, Erwin G; Clifford, Steven C; Bourdeaut, Franck; Delattre, Olivier; Doz, François F; Hawkins, Cynthia E; Malkin, David; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T; Pfister, Stefan M; Taylor, Michael D

2014-03-20

Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

Identifying prognostic signature in ovarian cancer using DirGenerank

PubMed Central

Wang, Jian-Yong; Chen, Ling-Ling; Zhou, Xiong-Hui

2017-01-01

Identifying the prognostic genes in cancer is essential not only for the treatment of cancer patients, but also for drug discovery. However, it's still a big challenge to select the prognostic genes that can distinguish the risk of cancer patients across various data sets because of tumor heterogeneity. In this situation, the selected genes whose expression levels are statistically related to prognostic risks may be passengers. In this paper, based on gene expression data and prognostic data of ovarian cancer patients, we used conditional mutual information to construct gene dependency network in which the nodes (genes) with more out-degrees have more chances to be the modulators of cancer prognosis. After that, we proposed DirGenerank (Generank in direct netowrk) algorithm, which concerns both the gene dependency network and genes’ correlations to prognostic risks, to identify the gene signature that can predict the prognostic risks of ovarian cancer patients. Using ovarian cancer data set from TCGA (The Cancer Genome Atlas) as training data set, 40 genes with the highest importance were selected as prognostic signature. Survival analysis of these patients divided by the prognostic signature in testing data set and four independent data sets showed the signature can distinguish the prognostic risks of cancer patients significantly. Enrichment analysis of the signature with curated cancer genes and the drugs selected by CMAP showed the genes in the signature may be drug targets for therapy. In summary, we have proposed a useful pipeline to identify prognostic genes of cancer patients. PMID:28615526

Colorectal cancer screening and adverse childhood experiences: Which adversities matter?

PubMed

Alcalá, Héctor E; Keim-Malpass, Jessica; Mitchell, Emma

2017-07-01

Adverse Childhood Experiences (ACEs) have been associated with an increased risk of a variety of diseases, including cancer. However, research has not paid enough attention to the association between ACEs and cancer screening. As such, the present study examined the association between ACEs and ever using colorectal cancer (CRC) screening, among adults age 50 and over. Analyses used the 2011 Behavioral Risk Factor Surveillance System (n=24,938) to model odds of ever engaging in CRC screening from nine different adversities. Bivariate and multivariate models were fit. In bivariate models, physical abuse, having parents that were divorced or separated, and living in a household where adults treated each other violently were associated with lower odds of engaging in CRC. In multivariate models that accounted for potential confounders, emotional and sexual abuse were each associated with higher odds of engaging in CRC. Results suggest potential pathways by which early childhood experiences can impact future health behaviors. Future research should examine this association longitudinally. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prognostic significance of hyperfibrinogenemia in patients with esophageal squamous cell carcinoma.

PubMed

Suzuki, Takashi; Shimada, Hideaki; Nanami, Tatsuki; Oshima, Yoko; Yajima, Satoshi; Washizawa, Naohiro; Kaneko, Hironori

2017-06-01

Preoperative hyperfibrinogenemia is associated with inflammatory mediators and a poor prognosis in several types of cancer. However, there is no published information on the monitoring of patients with preoperative hyperfibrinogenemia after surgery. The aim of the study reported here was to assess the clinicopathological and prognostic significance of plasma fibrinogen levels in patients with esophageal squamous cell carcinoma before and after surgical treatment. Plasma fibrinogen levels were analyzed before surgical treatment (endoscopic submucosal dissection and surgery) in 82 patients with esophageal squamous cell carcinoma. The clinicopathological significance of plasma fibrinogen levels and the relationship of plasma fibrinogen levels with several biomarkers were evaluated. The cutoff value for hyperfibrinogenemia was 321 mg/dl. Univariate and multivariate analysis using the Cox proportional hazards model were performed to evaluate the prognostic significance of plasma fibrinogen levels. The changing patterns of plasma fibrinogen were monitored after surgical treatment to evaluate prognostic impact. Hyperfibrinogenemia was significantly associated with advanced pathological stage of cancer and high C-reactive protein levels. Plasma fibrinogen levels significantly decreased after surgical treatment in recurrence-free patients but did not decrease in patients with recurrence. The multivariate analysis indicated that preoperative hyperfibrinogenemia was an independent prognostic factor for poor survival (hazard ratio 1.005, 95% confidence interval 1.000-1.010; P = 0.039). Preoperative hyperfibrinogenemia was associated with inflammatory mediators, tumor progression, and poor survival in patients with esophageal squamous cell carcinoma. The absence of a decrease in plasma fibrinogen levels after surgical treatment may indicate the possibility of tumor recurrence.

Prognostic analysis of patients with epilepsy according to time of relapse after withdrawal of antiepileptic drugs following four seizure-free years.

PubMed

Park, Soochul; Lee, Dong Hyun; Kim, Seung Woo; Roh, Yun Ho

2017-01-01

We performed a retrospective, prognostic analysis of a cohort of patients with epilepsy according to time of relapse after four seizure-free years. Planned withdrawal of antiepileptic drugs (AEDs) and at least 3 years of follow-up after AED discontinuation were performed. The following two groups were assessed: (1) an early relapse (ER) group of patients who experienced recurrence during AED withdrawal and (2) a late relapse (LR) group of patients who experienced recurrence after completion of the AED discontinuation process. After dichotomization, the relapse rate, prognostic factors, and their impacts for each group were compared with those of a group of patients who continued to be seizure-free after AED withdrawal (SF group) using multiple logistic regression analysis. The AED intake mode was also analyzed. Two hundred seventeen (64.6%) of the 336 total patients experienced relapse. One hundred thirty-nine patients (41.4%) and 78 patients (23.2%) were included in the LR and ER groups, respectively. Symptom duration >120 months showed the strongest negative prognostic impact as demonstrated by the 4.7-fold higher risk of recurrence in the ER group compared with the SF group. Additional factors with a negative prognostic impact included an age at epilepsy onset of ≤20 years and the presence of localization-related epilepsy. No reliable predictor between the SF and LR groups was revealed. After exclusion of the SF group, post hoc analysis according to age at epilepsy onset and symptom duration showed that the above-mentioned negative prognostic factors significantly affected the relapse patterns of the LR and ER groups. The results suggest that longer symptom duration, which could be associated with intrinsic reactivation of epilepsy, is the strongest negative prognostic factor for relapse. Relapse after AED withdrawal in prolonged follow-up of seizure-free patients is one aspect of the natural history of epilepsy. © 2016 The Authors. Epilepsia published by

Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia.

PubMed

Such, Esperanza; Germing, Ulrich; Malcovati, Luca; Cervera, José; Kuendgen, Andrea; Della Porta, Matteo G; Nomdedeu, Benet; Arenillas, Leonor; Luño, Elisa; Xicoy, Blanca; Amigo, Mari L; Valcarcel, David; Nachtkamp, Kathrin; Ambaglio, Ilaria; Hildebrandt, Barbara; Lorenzo, Ignacio; Cazzola, Mario; Sanz, Guillermo

2013-04-11

The natural course of chronic myelomonocytic leukemia (CMML) is highly variable but a widely accepted prognostic scoring system for patients with CMML is not available. The main aim of this study was to develop a new CMML-specific prognostic scoring system (CPSS) in a large series of 558 patients with CMML (training cohort, Spanish Group of Myelodysplastic Syndromes) and to validate it in an independent series of 274 patients (validation cohort, Heinrich Heine University Hospital, Düsseldorf, Germany, and San Matteo Hospital, Pavia, Italy). The most relevant variables for overall survival (OS) and evolution to acute myeloblastic leukemia (AML) were FAB and WHO CMML subtypes, CMML-specific cytogenetic risk classification, and red blood cell (RBC) transfusion dependency. CPSS was able to segregate patients into 4 clearly different risk groups for OS (P < .001) and risk of AML evolution (P < .001) and its predictive capability was confirmed in the validation cohort. An alternative CPSS with hemoglobin instead of RBC transfusion dependency offered almost identical prognostic capability. This study confirms the prognostic impact of FAB and WHO subtypes, recognizes the importance of RBC transfusion dependency and cytogenetics, and offers a simple and powerful CPSS for accurately assessing prognosis and planning therapy in patients with CMML.

The Prognostic Value of the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging System in HER2-Enriched Subtype Breast Cancer, a Retrospective Analysis.

PubMed

Zhou, Bin; Xu, Ling; Ye, Jingming; Xin, Ling; Duan, Xuening; Liu, Yinhua

2017-08-01

The American Joint Committee on Cancer (AJCC) released its 8th edition of tumor staging which is to be implemented in early 2018. The present study aimed to analyze the prognostic value of AJCC 8th edition Cancer Staging System in HER2-enriched breast cancer, on a retrospective cohort. This study was a retrospective single-center study of HER2-enriched breast cancer cases diagnosed from January 2008 to December 2014. Clinicopathological features and follow up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore prognostic factors for disease outcome. We restaged patients based on the 8th edition of the AJCC cancer staging system and analyzed prognostic value of the Anatomic Stage Group and the Prognostic Stage Group. The study enrolled 170 HER2-enriched subtype breast cancer patients with 5-year disease free survival (DFS) of 85.1% and 5-year overall survival (OS) of 86.8%. Prognostic stages of 117 cases (68.8%) changed compared with anatomic stages, with 116 upstaged cases and 1 downstaged case. The Anatomic Stage Groups had a significant prognostic impact on DFS (χ 2 =16.752, p<0.001) and OS (χ 2 =25.038, p<0.001). The Prognostic Staging Groups had a significant prognostic impact on DFS (χ 2 =6.577, p=0.037) and OS (χ 2 =21.762, p<0.001). In the multivariate analysis, both stage groups were independent predictors of OS. Both Anatomic and Prognostic Stage Groups in the 8th edition of the AJCC breast cancer staging system had prognostic value in HER2-enriched subtype breast cancer. The Prognostic Stage system was a breakthrough on the basis of anatomic staging system. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer.

PubMed

Goltz, Diane; Montani, Matteo; Braun, Martin; Perner, Sven; Wernert, Nicolas; Jung, Klaus; Dietel, Manfred; Stephan, Carsten; Kristiansen, Glen

2015-12-01

We evaluated the prognostic value of the mitosis-associated marker phosphorylated histone H3 (PHH3) and Ki-67 in prostate cancer with respect to ERG status and androgen receptor (AR) expression.PHH3 and Ki-67 expression was immunohistochemically detected and digitally quantitated in a radical prostatectomy cohort (n = 640). The results were correlated to clinicopathological parameters including biochemical recurrence times. Prognostic values of PHH3 and Ki-67 were analysed by Cox regression and Kaplan-Meier statistics.In prostate cancer, mean Ki-67 and PHH3 rates were 3.40% (95%CI 3.16-3.63%) and 0.0152% (95%CI 0.0112-0.0191%), respectively.Ki-67 showed a significant correlation with Gleason scores, pT status, margin status, and AR expression, while PHH3 showed a significant correlation with Gleason scores and pT status. Univariate analyses for biochemical recurrence times demonstrated a significant prognostic value for median Ki-67 rate and for the PHH3 rate of the 90th percentile. Of importance, in patient subgroups stratified according to AR expression and ERG translocation, the prognostic power of proliferation markers PHH3 and Ki-67 was markedly enhanced in ERG translocation negative and high-level AR expressing ERG translocation positive prostate cancers.As expected, the proliferation markers PHH3 and Ki-67 predict adverse outcome of prostate cancer and have a particularly pronounced prognostic value in specific molecular subsets of prostate cancer (ERG- or AR+).

Adverse effects of public health interventions: a conceptual framework.

PubMed

Lorenc, Theo; Oliver, Kathryn

2014-03-01

Public health interventions may have a range of adverse effects. However, there is limited guidance as to how evaluations should address the possibility of adverse effects. This discussion paper briefly presents a framework for thinking about the potential harms of public health interventions, focusing on the following categories: direct harms; psychological harms; equity harms; group and social harms; and opportunity harms. We conclude that the possibility of adverse effects needs to be taken into account by those implementing and evaluating interventions, and requires a broad perspective on the potential impacts of public health strategies.

Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications.

PubMed

Balafoutas, Dimitrios; zur Hausen, Axel; Mayer, Sebastian; Hirschfeld, Marc; Jaeger, Markus; Denschlag, Dominik; Gitsch, Gerald; Jungbluth, Achim; Stickeler, Elmar

2013-06-03

Cancer-testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors. The reactivity pattern of various mAbs (6C1, MA454, M3H67, 57B, E978, GAGE #26 and NY-BR-1 #5) were assessed by immunohistochemistry in a tissue micro array series of 210 randomly selected primary invasive breast cancers in order to study the diversity of different CTAs (e.g. MAGE-A, NY-ESO-1, GAGE) and NY-BR-1. These expression data were correlated to clinico-pathological parameters and outcome data including disease-free and overall survival. Expression of at least one CTA was detectable in the cytoplasm of tumor cells in 37.2% of the cases. NY-BR-1 expression was found in 46.6% of tumors, respectively. Overall, CTA expression seemed to be linked to adverse prognosis and M3H67 immunoreactivity specifically was significantly correlated to shorter overall and disease-free survival (p=0.000 and 0.024, respectively). Our findings suggest that M3H67 immunoreactivity could serve as potential prognostic marker in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define new targets for specific breast cancer therapies.

Integration of Wall Motion, Coronary Flow Velocity, and Left Ventricular Contractile Reserve in a Single Test: Prognostic Value of Vasodilator Stress Echocardiography in Patients with Diabetes.

PubMed

Cortigiani, Lauro; Huqi, Alda; Ciampi, Quirino; Bombardini, Tonino; Bovenzi, Francesco; Picano, Eugenio

2018-06-01

Coronary flow velocity reserve (CFVR) and left ventricular contractile reserve (LVCR) have demonstrated prognostic importance in patients with diabetes. The aim of this study was to investigate the prognostic contribution of combined evaluation of CFVR and LVCR in patients with diabetes with nonischemic stress echocardiography. Three hundred seventy-five patients with diabetes (mean age, 68 ± 9 years) with nonischemic dipyridamole stress echocardiography underwent assessment of CFVR of the left anterior descending coronary artery (prospectively) and LVCR with left ventricular force (retrospectively) in a multicenter study. On receiver operating characteristic analysis, LVCR ≤ 1.1 was the best prognostic predictor and was considered an abnormal value. CFVR was abnormal (≤2) in 139 patients (37%), LVCR in 156 (42%), neither in 157 (42%), and both in 77 (21%). During a median follow-up period of 16 months, 86 major adverse cardiac events occurred: 16 deaths, 13 myocardial infarctions, and 57 revascularizations. Multivariate prognostic indicators were CFVR ≤ 2 (P < .0001), age (P = .03), and LVCR ≤ 1.1 (P = .04). The 3-year rate of major adverse cardiac events was 63% in patients with both abnormal CFVR and LVCR, 42% in those with abnormal CFVR only, 19% in those with abnormal LVCR only, and 10% in patients with both normal CFVR and LVCR. The 3-year hard event rate was 3% in patients with both normal CFVR and LVCR, fivefold higher in patients with abnormal CFVR or LVCR only, and ninefold higher in patients with both abnormal CFVR and LVCR. Patients with diabetes with nonischemic dipyridamole stress echocardiography may still have significant risk in presence of abnormal CFVR and/or LVCR, which assess the underlying, largely unrelated, microvascular and myocardial components of coronary circulation. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Prognostic significance of DSG3 in rectal adenocarcinoma treated with preoperative chemoradiotherapy.

PubMed

Chao, Tung-Bo; Li, Chien-Feng; Lin, Ching-Yih; Tian, Yu-Feng; Chang, I-Wei; Sheu, Ming-Jen; Lee, Ying-En; Chan, Ti-Chun; He, Hong-Lin

2016-06-01

This study aimed to investigate the prognostic significance of DSG3 and its association with response to neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer. Data mining of a publicly available dataset was performed to find genes associated with CCRT response. Immunohistochemistry was applied to evaluate DSG3 expression. The relationships between DSG3 expression and various clinicopathological parameters and survival were analyzed. The DSG3 gene was significantly associated with CCRT response. The expression of DSG3 negatively correlated with poorer tumor regression (p < 0.001) and had an independent negative impact on disease-specific survival (p = 0.011), local recurrence-free survival (p = 0.031) and metastasis-free survival (p = 0.029). DSG3 was a key prognostic factor and predictor for CCRT response in rectal cancer patients.

Prognosis Research Strategy (PROGRESS) 2: prognostic factor research.

PubMed

Riley, Richard D; Hayden, Jill A; Steyerberg, Ewout W; Moons, Karel G M; Abrams, Keith; Kyzas, Panayiotis A; Malats, Núria; Briggs, Andrew; Schroter, Sara; Altman, Douglas G; Hemingway, Harry

2013-01-01

Prognostic factor research aims to identify factors associated with subsequent clinical outcome in people with a particular disease or health condition. In this article, the second in the PROGRESS series, the authors discuss the role of prognostic factors in current clinical practice, randomised trials, and developing new interventions, and explain why and how prognostic factor research should be improved.

Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo

2014-07-01

Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months,more » the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.« less

Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications

PubMed Central

Kimbung, Siker; Kovács, Anikó; Danielsson, Anna; Bendahl, Pär-Ola; Lövgren, Kristina; Stolt, Marianne Frostvik; Tobin, Nicholas P.; Lindström, Linda; Bergh, Jonas; Einbeigi, Zakaria; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2015-01-01

The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. PMID:26375671

Prognostic Factors for Persistent Leg-Pain in Patients Hospitalized With Acute Sciatica.

PubMed

Fjeld, Olaf; Grotle, Margreth; Siewers, Vibeke; Pedersen, Linda M; Nilsen, Kristian Bernhard; Zwart, John-Anker

2017-03-01

Prospective cohort study. To identify potential prognostic factors for persistent leg-pain at 12 months among patients hospitalized with acute severe sciatica. The long-term outcome for patients admitted to hospital with sciatica is generally unfavorable. Results concerning prognostic factors for persistent sciatica are limited and conflicting. A total of 210 patients acutely admitted to hospital for either surgical or nonsurgical treatment of sciatica were consecutively recruited and received a thorough clinical and radiographic examination in addition to responding to a comprehensive questionnaire. Follow-up assessments were done at 6 weeks, 6 months, and 12 months. Potential prognostic factors were measured at baseline and at 6 weeks. The impact of these factors on leg-pain was analyzed by multiple linear regression modeling. A total of 151 patients completed the entire study, 93 receiving nonrandomized surgical treatment. The final multivariate models showed that the following factors were significantly associated with leg-pain at 12 months: high psychosocial risk according to the Örebro Musculosceletal Pain Questionnaire (unstandardized beta coefficient 1.55, 95% confidence interval [CI] 0.72-2.38, P < 0.001), not receiving surgical treatment (1.11, 95% CI 0.29-1.93, P = 0.01), not actively employed upon admission (1.47, 95% CI 0.63-2.31, P < 0.01), and self-reported leg-pain recorded 6 weeks posthospital admission (0.49, 95% CI 0.34-0.63, P < 0.001). Interaction analysis showed that the Örebro Musculosceletal Pain Questionnaire had significant prognostic value only on the nonsurgically treated patients (3.26, 95% CI 1.89-4.63, P < 0.001). The results suggest that a psychosocial screening tool and the implementation of a 6-week postadmission follow-up has prognostic value in the hospital management of severe sciatica. 2.

Environmental adversities and psychotic symptoms: The impact of timing of trauma, abuse, and neglect.

PubMed

Schalinski, Inga; Breinlinger, Susanne; Hirt, Vanessa; Teicher, Martin H; Odenwald, Michael; Rockstroh, Brigitte

2017-11-13

Trauma and adverse childhood experiences (ACE) occur more often in mental illness, including psychosis, than in the general population. Individuals with psychosis (cases) report a higher number and severity (dose) of adversities than healthy controls. While a dose-dependent increase of adversities has been related to more severe psychopathology, the role of type and timing is still insufficiently understood on the exacerbation of positive and negative psychotic symptoms. Moreover, dissociative symptoms were examined as potential mediator between adversities and severity of psychotic symptoms. Exposure to adversities were assessed by interviews in n=180 cases and n=70 controls. In cases, symptom severities were obtained for psychotic symptoms and dissociation. Conditioned random forest regression determined the importance of type and timing of ACE for positive and negative symptom severity, and mediator analyses evaluated the role of dissociative symptoms in the relationship between adversities and psychotic symptoms. Cases experienced substantially more abuse and neglect than controls. Adversities were related in a dose-dependent manner to psychotic disorder. An array of adversities was associated with more severe positive symptoms, while the conditioned random forest regression depicted neglect at age 10 as the most important predictor. Dissociative symptoms mediated the small relation of trauma load in childhood and positive symptoms. The role of trauma and ACE on psychotic symptoms can be specified by neglect during frontocortical development in the exacerbation of positive symptoms. The mediating role of dissociation is restricted to the relation of childhood trauma and positive symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Body Mass Index Influences the Prognostic Impact of Combined Nuclear Insulin Receptor and Estrogen Receptor Expression in Primary Breast Cancer.

PubMed

Björner, Sofie; Rosendahl, Ann H; Simonsson, Maria; Markkula, Andrea; Jirström, Karin; Borgquist, Signe; Rose, Carsten; Ingvar, Christian; Jernström, Helena

2017-01-01

The prognostic importance of tumor-specific nuclear insulin receptor (InsR) expression in breast cancer is unclear, while membrane and cytoplasmic localization of InsR is better characterized. The insulin signaling network is influenced by obesity and may interact with the estrogen receptor α (ERα) signaling. The purpose was to investigate the interplay between nuclear InsR, ER, body mass index (BMI), and prognosis. Tumor-specific expression of nuclear InsR was evaluated by immunohistochemistry in tissue microarrays from 900 patients with primary invasive breast cancer without preoperative treatment, included in a population-based cohort in Sweden (2002-2012) in relation to prognosis. Patients were followed for up to 11 years during which 107 recurrences were observed. Nuclear InsR + expression was present in 214 patients (23.8%) and increased with longer time between surgery and staining ( P  < 0.001). There were significant effect modifications by ER status and BMI in relation to clinical outcomes. Nuclear InsR + conferred higher recurrence-risk in patients with ER + tumors, but lower risk in patients with ER - tumors ( P interaction  = 0.003). Normal-weight patients with nuclear InsR + tumors had higher recurrence-risk, while overweight or obese patients had half the recurrence-risk compared to patients with nuclear InsR - tumors ( P interaction  = 0.007). Normal-weight patients with a nuclear InsR - /ER + tumor had the lowest risk for recurrence compared to all other nuclear InsR/ER combinations [HR adj 0.50, 95% confidence interval (CI): 0.25-0.97], while overweight or obese patients with nuclear InsR - /ER - tumors had the worst prognosis (HR adj 7.75, 95% CI: 2.04-29.48). Nuclear InsR was more prognostic than ER among chemotherapy-treated patients. In summary, nuclear InsR may have prognostic impact among normal-weight patients with ER + tumors and in overweight or obese patients with ER - tumors. Normal-weight patients with nuclear Ins

Prognostic Disclosures to Children: A Historical Perspective.

PubMed

Sisk, Bryan A; Bluebond-Langner, Myra; Wiener, Lori; Mack, Jennifer; Wolfe, Joanne

2016-09-01

Prognostic disclosure to children has perpetually challenged clinicians and parents. In this article, we review the historical literature on prognostic disclosure to children in the United States using cancer as an illness model. Before 1948, there was virtually no literature focused on prognostic disclosure to children. As articles began to be published in the 1950s and 1960s, many clinicians and researchers initially recommended a "protective" approach to disclosure, where children were shielded from the harms of bad news. We identified 4 main arguments in the literature at this time supporting this "protective" approach. By the late 1960s, however, a growing number of clinicians and researchers were recommending a more "open" approach, where children were included in discussions of diagnosis, which at the time was often synonymous with a terminal prognosis. Four different arguments in the literature were used at this time supporting this "open" approach. Then, by the late 1980s, the recommended approach to prognostic disclosure in pediatrics shifted largely from "never tell" to "always tell." In recent years, however, there has been a growing appreciation for the complexity of prognostic disclosure in pediatrics. Current understanding of pediatric disclosure does not lead to simple "black-and-white" recommendations for disclosure practices. As with most difficult questions, we are left to balance competing factors on a case-by-case basis. We highlight 4 categories of current considerations related to prognostic disclosure in pediatrics, and we offer several approaches to prognostic disclosure for clinicians who care for these young patients and their families. Copyright © 2016 by the American Academy of Pediatrics.

Conceptualizing prognostic awareness in advanced cancer: a systematic review.

PubMed

Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

2014-09-01

This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients' understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. © The Author(s) 2013.

Conceptualizing prognostic awareness in advanced cancer: A systematic review

PubMed Central

Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

2015-01-01

This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients’ understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. PMID:24157936

BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms: a prospective study.

PubMed

Buchmann, Arlette F; Hellweg, Rainer; Rietschel, Marcella; Treutlein, Jens; Witt, Stephanie H; Zimmermann, Ulrich S; Schmidt, Martin H; Esser, Günter; Banaschewski, Tobias; Laucht, Manfred; Deuschle, Michael

2013-08-01

Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val⁶⁶Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val⁶⁶Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val⁶⁶Met and 5-HTTLPR genotype. Copyright © 2013. Published by Elsevier B.V.

Cytogenetic Prognostication Within Medulloblastoma Subgroups

PubMed Central

Shih, David J.H.; Northcott, Paul A.; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M.; Garzia, Livia; Peacock, John; Mack, Stephen C.; Wu, Xiaochong; Rolider, Adi; Morrissy, A. Sorana; Cavalli, Florence M.G.; Jones, David T.W.; Zitterbart, Karel; Faria, Claudia C.; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A.; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G.; Liau, Linda M.; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K.; Thompson, Reid C.; Bailey, Simon; Lindsey, Janet C.; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M.C.; Scherer, Stephen W.; Phillips, Joanna J.; Gupta, Nalin; Fan, Xing; Muraszko, Karin M.; Vibhakar, Rajeev; Eberhart, Charles G.; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J.; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F.; Weiss, William A.; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R.; Rubin, Joshua B.; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M.; Gajjar, Amar; Packer, Roger J.; Rutkowski, Stefan; Pomeroy, Scott L.; French, Pim J.; Kloosterhof, Nanne K.; Kros, Johan M.; Van Meir, Erwin G.; Clifford, Steven C.; Bourdeaut, Franck; Delattre, Olivier; Doz, François F.; Hawkins, Cynthia E.; Malkin, David; Grajkowska, Wieslawa A.; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

2014-01-01

Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID

Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

PubMed Central

Fabregat-Andrés, Óscar; Estornell-Erill, Jordi; Ridocci-Soriano, Francisco; Pérez-Boscá, José Leandro; García-González, Pilar; Payá-Serrano, Rafael; Morell, Salvador; Cortijo, Julio

2016-01-01

Background Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. Objective We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Methods Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. Results 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). Conclusions In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF. PMID:26840055

A consensus prognostic gene expression classifier for ER positive breast cancer

PubMed Central

Teschendorff, Andrew E; Naderi, Ali; Barbosa-Morais, Nuno L; Pinder, Sarah E; Ellis, Ian O; Aparicio, Sam; Brenton, James D; Caldas, Carlos

2006-01-01

Background A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer. Results Here we perform a combined analysis of three major breast cancer microarray data sets to hone in on a universally valid prognostic molecular classifier in estrogen receptor (ER) positive tumors. Using a recently developed robust measure of prognostic separation, we further validate the prognostic classifier in three external independent cohorts, confirming the validity of our molecular classifier in a total of 877 ER positive samples. Furthermore, we find that molecular classifiers may not outperform classical prognostic indices but that they can be used in hybrid molecular-pathological classification schemes to improve prognostic separation. Conclusion The prognostic molecular classifier presented here is the first to be valid in over 877 ER positive breast cancer samples and across three different microarray platforms. Larger multi-institutional studies will be needed to fully determine the added prognostic value of molecular classifiers when combined with standard prognostic factors. PMID:17076897

Prognostic Value of Urinary Neutrophil Gelatinase-Associated Lipocalin on the First Day of Admission for Adverse Events in Patients With Acute Decompensated Heart Failure.

PubMed

Nakada, Yasuki; Kawakami, Rika; Matsui, Masaru; Ueda, Tomoya; Nakano, Tomoya; Takitsume, Akihiro; Nakagawa, Hitoshi; Nishida, Taku; Onoue, Kenji; Soeda, Tsunenari; Okayama, Satoshi; Watanabe, Makoto; Kawata, Hiroyuki; Okura, Hiroyuki; Saito, Yoshihiko

2017-05-18

Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) is an early predictor of acute kidney injury and adverse events in various diseases; however, in acute decompensated heart failure patients, its significance remains poorly understood. This study aimed to investigate the prognostic value of U-NGAL on the first day of admission for the occurrence of acute kidney injury and long-term outcomes in acute decompensated heart failure patients. We studied 260 acute decompensated heart failure patients admitted to our department between 2011 and 2014 by measuring U-NGAL in 24-hour urine samples collected on the first day of admission. Primary end points were all-cause death, cardiovascular death, and heart failure admission. Patients were divided into 2 groups according to their median U-NGAL levels (32.5 μg/gCr). The high-U-NGAL group had a significantly higher occurrence of acute kidney injury during hospitalization than the low-U-NGAL group ( P =0.0012). Kaplan-Meier analysis revealed that the high-U-NGAL group exhibited a worse prognosis than the low-U-NGAL group in all-cause death (hazard ratio 2.07; 95%CI 1.38-3.12, P =0.0004), cardiovascular death (hazard ratio 2.29; 95%CI 1.28-4.24, P =0.0052), and heart failure admission (hazard ratio 1.77; 95%CI 1.13-2.77, P =0.0119). The addition of U-NGAL to the estimated glomerular filtration rate significantly improved the predictive accuracy of all-cause mortality ( P =0.0083). In acute decompensated heart failure patients, an elevated U-NGAL level on the first day of admission was related to the development of clinical acute kidney injury and independently associated with poor prognosis. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Standardizing the definition of adverse pathology for lower risk men undergoing radical prostatectomy.

PubMed

Kozminski, Michael A; Tomlins, Scott; Cole, Adam; Singhal, Udit; Lu, Louis; Skolarus, Ted A; Palapattu, Ganesh S; Montgomery, Jeffrey S; Weizer, Alon Z; Mehra, Rohit; Hollenbeck, Brent K; Miller, David C; He, Chang; Feng, Felix Y; Morgan, Todd M

2016-09-01

Numerous definitions of adverse pathology at radical prostatectomy (RP) have been proposed and implemented for both research and clinical care, and there is tremendous variation in the specific criteria used to define adverse pathology in these settings. Given the current landscape in which magnetic resonance imaging criteria and biomarker cutoffs are validated for disparate adverse pathology definitions, we sought to identify which of these is most closely tied to biochemical recurrence (BCR) after RP. A total of 2,837 patients who underwent RP at a single institution for localized prostate cancer (PCa) were included. We evaluated the following existing definitions of adverse pathology at RP: (1) Gleason score ≥7, (2) primary Gleason pattern ≥4, (3) Gleason score ≥7 or pathologic stage T3-4, (4) pathologic stage T3-4, (5) primary Gleason pattern ≥4 or pathologic stage T3-4. The primary outcome measure was BCR. Multiple statistical techniques were used to assess BCR prediction. Of the 5 definitions assessed, 1 (primary Gleason pattern ≥4 or pathologic stage T3-4, 540 patients [19% of cohort]) consistently outperformed the other definitions across all statistical measures. Additionally, a total of only 13 (6.6%) and 34 (10.3%) men with very-low-risk and low-risk cancer per National Comprehensive Cancer Network guideline, respectively, met this definition of adverse pathology at the time of RP. Varying definitions of adverse pathology differ in their prognostic performance. The criteria defined by either primary Gleason pattern ≥4 or pT3-4 disease appears to most accurately predict BCR in this subset of patients with lower risk PCa at the time of diagnosis. Additionally, men with very-low-risk or low-risk PCa per National Comprehensive Cancer Network guidelines are relatively unlikely to have adverse pathology at the time of surgical resection. These data may help inform the use of imaging and molecular markers as well as the intensity of surveillance in

Adverse childhood experiences and health anxiety in adulthood.

PubMed

Reiser, Sarah J; McMillan, Katherine A; Wright, Kristi D; Asmundson, Gordon J G

2014-03-01

Childhood experiences are thought to predispose a person to the development of health anxiety later in life. However, there is a lack of research investigating the influence of specific adverse experiences (e.g., childhood abuse, household dysfunction) on this condition. The current study examined the cumulative influence of multiple types of childhood adversities on health anxiety in adulthood. Adults 18-59 years of age (N=264) completed a battery of measures to assess adverse childhood experiences, health anxiety, and associated constructs (i.e., negative affect and trait anxiety). Significant associations were observed between adverse childhood experiences, health anxiety, and associated constructs. Hierarchical multiple regression analysis indicted that adverse childhood experiences were predictive of health anxiety in adulthood; however, the unique contribution of these experience were no longer significant following the inclusion of the other variables of interest. Subsequently, mediation analyses indicated that both negative affect and trait anxiety independently mediated the relationship between adverse childhood experiences and health anxiety in adulthood. Increased exposure to adverse childhood experiences is associated with higher levels of health anxiety in adulthood; this relationship is mediated through negative affect and trait anxiety. Findings support the long-term negative impact of cumulative adverse childhood experiences and emphasize the importance of addressing negative affect and trait anxiety in efforts to prevent and treat health anxiety. Copyright © 2013 Elsevier Ltd. All rights reserved.

Modifiable Resilience Factors to Childhood Adversity for Clinical Pediatric Practice.

PubMed

Traub, Flora; Boynton-Jarrett, Renée

2017-05-01

Childhood adversity is highly prevalent and associated with risk for poor health outcomes in childhood and throughout the life course. Empirical literature on resilience over the past 40 years has identified protective factors for traumatized children that improve health outcomes. Despite these empirical investigations of resilience, there is limited integration of these findings into proactive strategies to mitigate the impact of adverse childhood experiences. We review the state of resilience research, with a focus on recent work, as it pertains to protecting children from the health impacts of early adversity. We identify and document evidence for 5 modifiable resilience factors to improve children's long- and short-term health outcomes, including fostering positive appraisal styles in children and bolstering executive function, improving parenting, supporting maternal mental health, teaching parents the importance of good self-care skills and consistent household routines, and offering anticipatory guidance about the impact of trauma on children. We conclude with 10 recommendations for pediatric practitioners to leverage the identified modifiable resilience factors to help children withstand, adapt to, and recover from adversity. Taken together, these recommendations constitute a blueprint for a trauma-informed medical home. Building resilience in pediatric patients offers an opportunity to improve the health and well-being of the next generation, enhance national productivity, and reduce spending on health care for chronic diseases. Copyright © 2017 by the American Academy of Pediatrics.

Incorporating prognostic imaging biomarkers into clinical practice

PubMed Central

Miles, Kenneth A.

2013-01-01

Abstract A prognostic imaging biomarker can be defined as an imaging characteristic that is objectively measurable and provides information on the likely outcome of the cancer disease in an untreated individual and should be distinguished from predictive imaging biomarkers and imaging markers of response. A range of tumour characteristics of potential prognostic value can be measured using a variety imaging modalities. However, none has currently been adopted into routine clinical practice. This article considers key examples of emerging prognostic imaging biomarkers and proposes an evaluation framework that aims to demonstrate clinical efficacy and so support their introduction into the clinical arena. With appropriate validation within an established evaluation framework, prognostic imaging biomarkers have the potential to contribute to individualized cancer care, in some cases reducing the financial burden of expensive cancer treatments by facilitating their more rational use. PMID:24060808

Early warning score independently predicts adverse outcome and mortality in patients with acute pancreatitis.

PubMed

Jones, Michael J; Neal, Christopher P; Ngu, Wee Sing; Dennison, Ashley R; Garcea, Giuseppe

2017-08-01

The aim of this study was to compare the prognostic value of established scoring systems with early warning scores in a large cohort of patients with acute pancreatitis. In patients presenting with acute pancreatitis, age, sex, American Society of Anaesthesiologists (ASA) grade, Modified Glasgow Score, Ranson criteria, APACHE II scores and early warning score (EWS) were recorded for the first 72 h following admission. These variables were compared between survivors and non-survivors, between patients with mild/moderate and severe pancreatitis (based on the 2012 Atlanta Classification) and between patients with a favourable or adverse outcome. A total of 629 patients were identified. EWS was the best predictor of adverse outcome amongst all of the assessed variables (area under curve (AUC) values 0.81, 0.84 and 0.83 for days 1, 2 and 3, respectively) and was the most accurate predictor of mortality on both days 2 and 3 (AUC values of 0.88 and 0.89, respectively). Multivariable analysis revealed that an EWS ≥2 was independently associated with severity of pancreatitis, adverse outcome and mortality. This study confirms the usefulness of EWS in predicting the outcome of acute pancreatitis. It should become the mainstay of risk stratification in patients with acute pancreatitis.

Prognostic value of tripartite motif containing 29 expression in patients with gastric cancer following surgical resection.

PubMed

Wang, Chenghu; Zhou, Yi; Chen, Beibei; Yuan, Weiwei; Huang, Jinxi

2018-04-01

Tripartite motif containing 29 (TRIM29) dysregulation serves an important function in the progression of numerous types of cancer, but its function in the prognosis of patients with gastric cancer remains unknown. The present study assessed the prognostic value of TRIM29 in patients with gastric cancer following surgical resection. A total of 243 fresh gastric adenocarcinoma and adjacent normal tissues were continuously retrieved from patients who underwent curative surgery for gastric cancer at the Cancer Hospital of Henan Province (Zhengzhou, China) between January 2005 and December 2011. The reverse transcription-quantitative polymerase chain reaction was performed to assess TRIM29 expression. The association between TRIM29 expression and clinicopathological features and prognosis was subsequently evaluated. The results of the present study revealed that the expression of TRIM29 was increased in the gastric cancer tissues compared with the normal adjacent tissues, and that upregulated expression of TRIM29 was associated with tumor cell differentiation, tumor stage, lymph node metastasis, and tumor-node-metastasis (TNM) stage. In the training and validation data, high TRIM29 expression was associated with poor overall survival in patients with gastric cancer. Furthermore, multivariate analysis identified that TRIM29 expression was an independent prognostic factor for overall survival, in addition to TNM stage and Lauren classification. Combining TRIM29 expression with the TNM staging system generated a novel predictive model that exhibited improved prognostic accuracy for overall survival in patients with gastric cancer. The present study revealed that TRIM29 was an independent adverse prognostic factor in patients with gastric cancer. Incorporating TRIM29 expression level into the TNM staging system may improve risk stratification and render prognosis more accurate in patients with gastric cancer.

Incidence, Prognostic Impact, and Predictive Factors of Readmission for Heart Failure After Transcatheter Aortic Valve Replacement.

PubMed

Durand, Eric; Doutriaux, Maxime; Bettinger, Nicolas; Tron, Christophe; Fauvel, Charles; Bauer, Fabrice; Dacher, Jean-Nicolas; Bouhzam, Najime; Litzler, Pierre-Yves; Cribier, Alain; Eltchaninoff, Hélène

2017-12-11

The aim of this study was to assess the incidence, prognostic impact, and predictive factors of readmission for congestive heart failure (CHF) in patients with severe aortic stenosis treated by transcatheter aortic valve replacement (TAVR). TAVR is indicated in patients with severe symptomatic aortic stenosis in whom surgery is considered high risk or is contraindicated. Readmission for CHF after TAVR remains a challenge, and data on prognostic and predictive factors are lacking. All patients who underwent TAVR from January 2010 to December 2014 were included. Follow-up was achieved for at least 1 year and included clinical and echocardiographic data. Readmission for CHF was analyzed retrospectively. This study included 546 patients, 534 (97.8%) of whom were implanted with balloon-expandable valves preferentially via the transfemoral approach in 87.8% of cases. After 1 year, 285 patients (52.2%) had been readmitted at least once, 132 (24.1%) for CHF. Patients readmitted for CHF had an increased risk for death (p < 0.0001) and cardiac death (p < 0.0001) compared with those not readmitted for CHF. On multivariate analysis, aortic mean gradient (hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.79 to 0.99; p = 0.03), post-procedural blood transfusion (HR: 2.27; 95% CI: 1.13 to 5.56; p = 0.009), severe post-procedural pulmonary hypertension (HR: 1.04; 95% CI: 1.00 to 1.07; p < 0.0001), and left atrial diameter (HR: 1.47; 95% CI: 1.08 to 2.01; p = 0.02) were independently associated with CHF readmission at 1 year. Readmission for CHF after TAVR was frequent and was strongly associated with 1-year mortality. Low gradient, persistent pulmonary hypertension, left atrial dilatation, and transfusions were predictive of readmission for CHF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

An Integrated Approach for Gear Health Prognostics

NASA Technical Reports Server (NTRS)

He, David; Bechhoefer, Eric; Dempsey, Paula; Ma, Jinghua

2012-01-01

In this paper, an integrated approach for gear health prognostics using particle filters is presented. The presented method effectively addresses the issues in applying particle filters to gear health prognostics by integrating several new components into a particle filter: (1) data mining based techniques to effectively define the degradation state transition and measurement functions using a one-dimensional health index obtained by whitening transform; (2) an unbiased l-step ahead RUL estimator updated with measurement errors. The feasibility of the presented prognostics method is validated using data from a spiral bevel gear case study.

Diagnosis of potential stressors adversely affecting benthic ...

EPA Pesticide Factsheets

Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was impaired. Second, the presence of source, stressor, and effect were established. Then linkages between source, stressor, and effect were developed. This allows identification of probable stressors adversely affecting the waterbody. Three pollutant categories were assessed: chemicals, nutrients, and suspended sediments. This weight of evidence approach indicated that Greenwich Bay was primarily impacted by eutrophication-related stressors. The sediments of Greenwich Bay were carbon enriched and low dissolved oxygen concentrations were commonly seen, especially in the western portions of Greenwich Bay. The benthic community was depauperate, as would be expected under oxygen stress. Although our analysis indicated that contaminant loads in Greenwich Bay were at concentrations where adverse effects might be expected, no toxicity was observed, as a result of high levels of organic carbon in these sediments reducing contaminant bioavailability. Our analysis also indicated that suspended sediment impacts were likely nonexistent for much of the Bay. This analysis demonstrates that the diagnostic procedure was useful to organize and assess the potential stressors impacting the ecological well-being

The impact of adverse events on health care costs for older adults undergoing nonelective abdominal surgery.

PubMed

Bailey, Jonathan G; Davis, Philip J B; Levy, Adrian R; Molinari, Michele; Johnson, Paul M

2016-06-01

Postoperative complications have been identified as an important and potentially preventable cause of increased hospital costs. While older adults are at increased risk of experiencing complications and other adverse events, very little research has specifically examined how these events impact inpatient costs. We sought to examine the association between postoperative complications, hospital mortality and loss of independence and direct inpatient health care costs in patients 70 years or older who underwent nonelective abdominal surgery. We prospectively enrolled consecutive patients 70 years or older who underwent nonelective abdominal surgery between July 1, 2011, and Sept. 30, 2012. Detailed patient-level data were collected regarding demographics, diagnosis, treatment and outcomes. Patient-level resource tracking was used to calculate direct hospital costs (2012 $CDN). We examined the association between complications, hospital mortality and loss of independence cost using multiple linear regression. During the study period 212 patients underwent surgery. Overall, 51.9% of patients experienced a nonfatal complication (32.5% minor and 19.4% major), 6.6% died in hospital and 22.6% experienced a loss of independence. On multivariate analysis nonfatal complications (p < 0.001), hospital mortality (p = 0.021) and loss of independence at discharge (p < 0.001) were independently associated with health care costs. These adverse events respectively accounted for 30%, 4% and 10% of the total costs of hospital care. Adverse events were common after abdominal surgery in older adults and accounted for 44% of overall costs. This represents a substantial opportunity for better patient outcomes and cost savings with quality improvement strategies tailored to the needs of this high-risk surgical population.

Prognostic Impact of Primary Tumor Location on Clinical Outcomes of Metastatic Colorectal Cancer Treated With Cetuximab Plus Oxaliplatin-Based Chemotherapy: A Subgroup Analysis of the JACCRO CC-05/06 Trials.

PubMed

Sunakawa, Yu; Ichikawa, Wataru; Tsuji, Akihito; Denda, Tadamichi; Segawa, Yoshihiko; Negoro, Yuji; Shimada, Ken; Kochi, Mitsugu; Nakamura, Masato; Kotaka, Masahito; Tanioka, Hiroaki; Takagane, Akinori; Tani, Satoshi; Yamaguchi, Tatsuro; Watanabe, Takanori; Takeuchi, Masahiro; Fujii, Masashi; Nakajima, Toshifusa

2017-09-01

Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy. The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022). Tumors proximal or from splenic flexure to rectum were defined as right-sided or left-sided, respectively. In addition, exploratory RAS and BRAF mutation analyses were performed. A total of 110 patients were assessable for tumor location; 90 had left-sided tumors. Left-sided tumors were significantly associated with longer overall survival (36.2 vs. 12.6 months, hazard ratio = 0.28, P < .0001) and progression-free survival (11.1 vs. 5.6 months, hazard ratio = 0.47, P = .0041) than right-sided tumors; similar results were obtained in multivariate analysis. A subanalysis showed that the association was evident in the FOLFOX group and that tumor location was an independent prognostic factor irrespective of BRAF status in RAS wild-type patients. Primary tumor location might be a predictor of survival independent of BRAF status in mCRC patients who receive first-line cetuximab combined with oxaliplatin-based chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Towards Prognostics of Electrolytic Capacitors

NASA Technical Reports Server (NTRS)

Celaya, Jose R.; Kulkarni, Chetan; Biswas, Gautam; Goegel, Kai

2011-01-01

A remaining useful life prediction algorithm and degradation model for electrolytic capacitors is presented. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management research. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. In particular, experimental results of an accelerated aging test under electrical stresses are presented. The capacitors used in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors.

Differential Prognostic Value of Coronary Computed Tomography Angiography in Relation to Exercise Electrocardiography in Asymptomatic Subjects

PubMed Central

Lee, Sang-Eun; Cho, Iksung; Hong, Geu-Ru; Sung, Ji Min; Cho, In-Jeong; Shim, Chi Young; Choi, Byoung Wook; Chung, Namsik

2015-01-01

Background To explore the prognostic performance of coronary computed tomography angiography (CCTA) and exercise electrocardiography (XECG) in asymptomatic subjects. Methods We retrospectively enrolled 812 (59 ± 9 years, 60.8% male) asymptomatic subjects who underwent CCTA and XECG concurrently from 2003 through 2009. Subjects were followed-up for major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, unstable angina, and revascularization after 90 days from index CCTA. Results The prevalence of occult coronary artery disease (CAD) detected by CCTA was 17.5% and 120 subjects (14.8%) had positive XECG. During a mean follow-up of 37 ± 16 months, nine subjects experienced MACE. In multivariable Cox-regression analysis, only the presence of CAD by CCTA independently predicted future MACE (p = 0.002). Moreover, CAD by CCTA improved the predictive value when added to a clinical risk factor model using the likelihood ratio test (p < 0.001). Notably, the prognostic value of CCTA persisted in the moderate-to-high-risk group as classified by the Duke treadmill score (p = 0.040), but not in the low-risk group (p = 0.991). Conclusion CCTA provides incremental prognostic benefit over and above XECG in an asymptomatic population, especially for those in a moderate-to-high-risk group as classified by the Duke treadmill score. Risk stratification using XECG may prove valuable for identifying asymptomatic subjects who can benefit from CCTA. PMID:26755933

Prognostic factors in prostate cancer.

PubMed

Braeckman, Johan; Michielsen, Dirk

2007-01-01

In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

FDG-PET/CT at the end of immuno-chemotherapy in follicular lymphoma: the prognostic role of the ratio between target lesion and liver SUVmax (rPET).

PubMed

Annunziata, Salvatore; Cuccaro, Annarosa; Tisi, Maria Chiara; Hohaus, Stefan; Rufini, Vittoria

2018-06-01

To retrospectively investigate the prognostic role of the ratio between target lesion and liver SUV max (rPET) in patients with follicular lymphoma (FL) submitted to FDG-PET/CT at the end of immuno-chemotherapy (PI-PET), and to compare rPET with International Harmonization Project criteria (IHP), Deauville Score (5p-DS) and FL International Prognostic Index at diagnosis (FLIPI). Eighty-nine patients with FL undergoing PI-PET were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point of rPET with respect to 5-years progression free survival (PFS). The prognostic significance of rPET was compared with IHP, DS and FLIPI. Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of adverse events as gold standard. The ROC analysis for rPET as predictor of progression showed an optimal rPET cut-point of 0.98. Patients with positive values of IHP, DS and rPET had a PFS of 50, 30 and 31%. PPV were of 56, 80 and 80%, NPV of 83, 86 and 88%, respectively. DS and rPET differed only in two patients. FLIPI was not predictive of progression and relapse. rPET is a prognostic factor in patients with FL submitted to PI-PET. Although it has a similar prognostic power as DS, it can have methodological advantages over visual analysis. PI-PET with different evaluation systems has a stronger prognostic power than FLIPI at diagnosis, so it could be useful to identify patients with FL at risk for early relapse after immuno-chemotherapy.

The Canadian Immunization Monitoring Program, ACTive (IMPACT): Active surveillance for vaccine adverse events and vaccine-preventable diseases

PubMed Central

Bettinger, JA; Halperin, SA; Vaudry, W; Law, BJ; Scheifele, DW

2014-01-01

For almost 25 years the Canadian Immunization Monitoring Program, ACTive (IMPACT) has been conducting active surveillance for severe adverse events following immunization (AEFIs) and vaccine-preventable diseases in children. The network, which consists of volunteer paediatric infectious diseases investigators at 12 tertiary care paediatric hospitals, is an important component of Canada’s AEFI monitoring. The network employs nurses at each of the sites to search for and report possible AEFIs to local, provincial and national public health authorities. The active nature of the surveillance ensures a high level of vigilance for severe AEFIs in children. PMID:29769912

Prognostic markers for colorectal cancer: estimating ploidy and stroma

PubMed Central

Danielsen, H E; Hveem, T S; Domingo, E; Pradhan, M; Kleppe, A; Syvertsen, R A; Kostolomov, I; Nesheim, J A; Askautrud, H A; Nesbakken, A; Lothe, R A; Svindland, A; Shepherd, N; Novelli, M; Johnstone, E; Tomlinson, I; Kerr, R; Kerr, D J

2018-01-01

Abstract Background We report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage colorectal cancer (CRC). Patients and methods DNA content (ploidy) and stroma-tumour fraction were estimated using automated digital imaging systems and DNA was extracted from sections of formalin-fixed paraffin-embedded (FFPE) tissue for analysis of microsatellite instability. Samples were available from 1092 patients recruited to the QUASAR 2 trial and two large observational series (Gloucester, n = 954; Oslo University Hospital, n = 578). Resultant biomarkers were analysed for prognostic impact using 5-year cancer-specific survival (CSS) as the clinical end point. Results Ploidy and stroma-tumour fraction were significantly prognostic in a multivariate model adjusted for age, adjuvant treatment, and pathological T-stage in stage II patients, and the combination of ploidy and stroma-tumour fraction was found to stratify these patients into three clinically useful groups; 5-year CSS 90% versus 83% versus 73% [hazard ratio (HR) = 1.77 (95% confidence interval (95% CI): 1.13–2.77) and HR = 2.95 (95% CI: 1.73–5.03), P < 0.001]. Conclusion A novel biomarker, combining estimates of ploidy and stroma-tumour fraction, sampled from FFPE tissue, identifies stage II CRC patients with low, intermediate or high risk of CRC disease specific death, and can reliably stratify clinically relevant patient sub-populations with differential risks of tumour recurrence and may support choice of adjuvant therapy for these individuals. PMID:29293881

Current state of prognostication and risk stratification in myelodysplastic syndromes.

PubMed

Zeidan, Amer M; Gore, Steven D; Padron, Eric; Komrokji, Rami S

2015-03-01

Myelodysplastic syndromes (MDS) are characterized by significant biologic and clinical heterogeneity. Because of the wide outcome variability, accurate prognostication is vital to high-quality risk-adaptive care of MDS patients. In this review, we discuss the current state of prognostic schemes for MDS and overview efforts aimed at utilizing molecular aberrations for prognostication in clinical practice. Several prognostic instruments have been developed and validated with increasing accuracy and complexity. Oncologists should be aware of the inherent limitations of these prognostic tools as they counsel patients and make clinical decisions. As more therapies are becoming available for MDS, the focus of model development is shifting from prognostic to treatment-specific predictive instruments. In addition to providing additional prognostic data beyond traditional clinical and pathologic parameters, the improved understanding of the genetic landscape and pathophysiologic consequences in MDS may allow the construction of treatment-specific predictive instruments. How to best use the results of molecular mutation testing to inform clinical decision making in MDS is still a work in progress. Important steps in this direction include standardization in performance and interpretation of assays and better understanding of the independent prognostic importance of the recurrent mutations, especially the less frequent ones.

Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma.

PubMed

Adams, Hugo J A; de Klerk, John M H; Fijnheer, Rob; Dubois, Stefan V; Nievelstein, Rutger A J; Kwee, Thomas C

2015-03-01

To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ=-0.042, P=0.765), categorized lactate dehydrogenase (LDH) ratio (ρ=0.201, P=0.156), extranodal disease in major organs (φ=-0.245, P=0.083), Ann Arbor stage III/IV disease (φ=-0.208, P=0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ=0.015, P=0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P=0.003) and overall survival (P=0.004). The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Individual differences in early adolescents' latent trait cortisol (LTC): Relation to early adversity.

PubMed

Stroud, Catherine B; Chen, Frances R; Doane, Leah D; Granger, Douglas A

2016-09-01

Substantial evidence suggests that youth who experience early adversity exhibit alterations in hypothalamic pituitary adrenal (HPA) axis functioning, thereby increasing risk for negative health outcomes. However, few studies have explored whether early adversity alters enduring trait indicators of HPA axis activity. Using objective contextual stress interviews with adolescents and their mothers to assess early adversity, we examined the cumulative impact of nine types of early adversity on early adolescents girls' latent trait cortisol (LTC). Adolescents (n = 122; M age = 12.39 years) provided salivary cortisol samples three times a day (waking, 30 min post-waking, and bedtime) over 3 days. Latent state-trait modeling indicated that the waking and 30 min post-waking samples contributed to a LTC factor. Moreover, greater early adversity was associated with a lower LTC level. Implications of LTC for future research examining the impact of early adversity on HPA axis functioning are discussed. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:700-713, 2016. © 2016 Wiley Periodicals, Inc.

Prognostic Analysis System and Methods of Operation

NASA Technical Reports Server (NTRS)

MacKey, Ryan M. E. (Inventor); Sneddon, Robert (Inventor)

2014-01-01

A prognostic analysis system and methods of operating the system are provided. In particular, a prognostic analysis system for the analysis of physical system health applicable to mechanical, electrical, chemical and optical systems and methods of operating the system are described herein.

Prognostics of Power MOSFET

NASA Technical Reports Server (NTRS)

Celaya, Jose Ramon; Saxena, Abhinav; Vashchenko, Vladislay; Saha, Sankalita; Goebel, Kai Frank

2011-01-01

This paper demonstrates how to apply prognostics to power MOSFETs (metal oxide field effect transistor). The methodology uses thermal cycling to age devices and Gaussian process regression to perform prognostics. The approach is validated with experiments on 100V power MOSFETs. The failure mechanism for the stress conditions is determined to be die-attachment degradation. Change in ON-state resistance is used as a precursor of failure due to its dependence on junction temperature. The experimental data is augmented with a finite element analysis simulation that is based on a two-transistor model. The simulation assists in the interpretation of the degradation phenomena and SOA (safe operation area) change.

An elevated neutrophil-lymphocyte ratio is associated with adverse outcomes following single time-point paracetamol (acetaminophen) overdose: a time-course analysis.

PubMed

Craig, Darren G; Kitto, Laura; Zafar, Sara; Reid, Thomas W D J; Martin, Kirsty G; Davidson, Janice S; Hayes, Peter C; Simpson, Kenneth J

2014-09-01

The innate immune system is profoundly dysregulated in paracetamol (acetaminophen)-induced liver injury. The neutrophil-lymphocyte ratio (NLR) is a simple bedside index with prognostic value in a number of inflammatory conditions. To evaluate the prognostic accuracy of the NLR in patients with significant liver injury following single time-point and staggered paracetamol overdoses. Time-course analysis of 100 single time-point and 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Timed laboratory samples were correlated with time elapsed after overdose or admission, respectively, and the NLR was calculated. A total of 49/100 single time-point patients developed hepatic encephalopathy (HE). Median NLRs were higher at both 72 (P=0.0047) and 96 h after overdose (P=0.0041) in single time-point patients who died or were transplanted. Maximum NLR values by 96 h were associated with increasing HE grade (P=0.0005). An NLR of more than 16.7 during the first 96 h following overdose was independently associated with the development of HE [odds ratio 5.65 (95% confidence interval 1.67-19.13), P=0.005]. Maximum NLR values by 96 h were strongly associated with the requirement for intracranial pressure monitoring (P<0.0001), renal replacement therapy (P=0.0002) and inotropic support (P=0.0005). In contrast, in the staggered overdose cohort, the NLR was not associated with adverse outcomes or death/transplantation either at admission or subsequently. The NLR is a simple test which is strongly associated with adverse outcomes following single time-point, but not staggered, paracetamol overdoses. Future studies should assess the value of incorporating the NLR into existing prognostic and triage indices of single time-point paracetamol overdose.

Impact of semaphorin expression on prognostic characteristics in breast cancer.

PubMed

Butti, Ramesh; Kumar, Totakura Vs; Nimma, Ramakrishna; Kundu, Gopal C

2018-01-01

Breast cancer is one of the major causes of cancer-related deaths among women worldwide. Aberrant regulation of various growth factors, cytokines, and other proteins and their receptors in cancer cells drives the activation of various oncogenic signaling pathways that lead to cancer progression. Semaphorins are a class of proteins which are differentially expressed in various types of cancer including breast cancer. Earlier, these proteins were known to have a major function in the nerve cell adhesion, migration, and development of the central nervous system. However, their role in the regulation of several aspects of tumor progression has eventually emerged. There are over 30 genes encoding the semaphorins, which are divided into eight subclasses. It has been reported that some members of semaphorin classes are antiangiogenic and antimetastatic in nature, whereas others act as proangiogenic and prometastatic genes. Because of their differential expression and role in angiogenesis and metastasis, semaphorins emerged as one of the important prognostic factors for appraising breast cancer progression.

Evaluating Algorithm Performance Metrics Tailored for Prognostics

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

2009-01-01

Prognostics has taken a center stage in Condition Based Maintenance (CBM) where it is desired to estimate Remaining Useful Life (RUL) of the system so that remedial measures may be taken in advance to avoid catastrophic events or unwanted downtimes. Validation of such predictions is an important but difficult proposition and a lack of appropriate evaluation methods renders prognostics meaningless. Evaluation methods currently used in the research community are not standardized and in many cases do not sufficiently assess key performance aspects expected out of a prognostics algorithm. In this paper we introduce several new evaluation metrics tailored for prognostics and show that they can effectively evaluate various algorithms as compared to other conventional metrics. Specifically four algorithms namely; Relevance Vector Machine (RVM), Gaussian Process Regression (GPR), Artificial Neural Network (ANN), and Polynomial Regression (PR) are compared. These algorithms vary in complexity and their ability to manage uncertainty around predicted estimates. Results show that the new metrics rank these algorithms in different manner and depending on the requirements and constraints suitable metrics may be chosen. Beyond these results, these metrics offer ideas about how metrics suitable to prognostics may be designed so that the evaluation procedure can be standardized. 1

A Distributed Prognostic Health Management Architecture

NASA Technical Reports Server (NTRS)

Bhaskar, Saha; Saha, Sankalita; Goebel, Kai

2009-01-01

This paper introduces a generic distributed prognostic health management (PHM) architecture with specific application to the electrical power systems domain. Current state-of-the-art PHM systems are mostly centralized in nature, where all the processing is reliant on a single processor. This can lead to loss of functionality in case of a crash of the central processor or monitor. Furthermore, with increases in the volume of sensor data as well as the complexity of algorithms, traditional centralized systems become unsuitable for successful deployment, and efficient distributed architectures are required. A distributed architecture though, is not effective unless there is an algorithmic framework to take advantage of its unique abilities. The health management paradigm envisaged here incorporates a heterogeneous set of system components monitored by a varied suite of sensors and a particle filtering (PF) framework that has the power and the flexibility to adapt to the different diagnostic and prognostic needs. Both the diagnostic and prognostic tasks are formulated as a particle filtering problem in order to explicitly represent and manage uncertainties; however, typically the complexity of the prognostic routine is higher than the computational power of one computational element ( CE). Individual CEs run diagnostic routines until the system variable being monitored crosses beyond a nominal threshold, upon which it coordinates with other networked CEs to run the prognostic routine in a distributed fashion. Implementation results from a network of distributed embedded devices monitoring a prototypical aircraft electrical power system are presented, where the CEs are Sun Microsystems Small Programmable Object Technology (SPOT) devices.

Parental personality as an inner resource that moderates the impact of ecological adversity on parenting.

PubMed

Kochanska, Grazyna; Aksan, Nazan; Penney, Sara J; Boldt, Lea J

2007-01-01

Parents' personality was examined as a moderator of the impact of demographic risk on parenting in a longitudinal study (N=102 families). Parents' personality and demographic risk (i.e., education level, age, family income, and family size) were assessed when children were infants, and parents' power assertion, warmth, and positive affect were observed in naturalistic interactions 2.5 years later. Parents' personality moderated the adverse impact of demographic risk on parenting. For parents who had memories of unstable and unhappy childhood experiences and who reported low conventionality, higher risk was linked to more power assertion, but there was no such link for those parents who recalled happy childhood experiences and who embraced conventions. For both parents who lacked a sense of optimism and social trust, and for fathers who reported low conventionality, higher risk was linked to less affectively positive parenting, but there was no such link for parents who were optimistic and trusting or for fathers who were conventional. Higher risk was linked to more power assertion, but only for mothers low in Extraversion and for fathers high in Neuroticism. 2007 APA, all rights reserved

Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis.

PubMed

Lee, Yee Mei; Lang, Dora; Lockwood, Craig

Increasing numbers of studies identify new prognostic factors for categorising chemotherapy-induced febrile neutropenia adult cancer patients into high- or low-risk groups for adverse outcomes. These groupings are used to tailor therapy according to level of risk. However many emerging factors with prognostic significance remain controversial, being based on single studies only. A systematic review was conducted to determine the strength of association of all identified factors associated with the outcomes of chemotherapy-induced febrile neutropenia patients. The participants included were adults of 15 years old and above, with a cancer diagnosis and who underwent cancer treatment.The review focused on clinical factors and their association with the outcomes of cancer patients with chemotherapy-induced febrile neutropenia at presentation of fever.All quantitative studies published in English which investigated clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia were considered.The primary outcome of interest was to identify the clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia. Electronic databases searched from their respective inception date up to December 2011 include MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Science-Direct, Scopus and Mednar. The quality of the included studies was subjected to assessment by two independent reviewers. The standardised critical appraisal tool from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used to assess the following criteria: representativeness of study population; clearly defined prognostic factors and outcomes; whether potential confounders were addressed and appropriate statistical analysis was undertaken for the study design. Data extraction was performed using a modified version of

The Glasgow Prognostic Score Predicts Response to Chemotherapy in Patients with Metastatic Breast Cancer.

PubMed

Wang, Dexing; Duan, Li; Tu, Zhiquan; Yan, Fei; Zhang, Cuicui; Li, Xu; Cao, Yuzhu; Wen, Hongsheng

2016-01-01

Breast cancer is one of the most common causes of cancer death in women worldwide. The Glasgow Prognostic Score (GPS), a cumulative prognostic score based on C-reactive protein and albumin, indicates the presence of a systemic inflammatory response. The GPS has been adopted as a powerful prognostic tool for patients with various types of malignant tumors, including breast cancer. The aim of this study was to assess the value of the GPS in predicting the response and toxicity in breast cancer patients treated with chemotherapy. Patients with metastatic breast cancers in a progressive stage for consideration of chemotherapy were eligible. The clinical characteristics and demographics were recorded. The GPS was calculated before the onset of chemotherapy. Data on the response to chemotherapy and progression-free survival (PFS) were also collected. Objective tumor responses were evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC) version 3.0 throughout therapy. In total, 106 breast cancer patients were recruited. The GPS was associated with the response rate (p = 0.05), the clinical benefit rate (p = 0.03), and PFS (p = 0.005). The GPS was the only independent predictor of PFS (p = 0.005). The GPS was significantly associated with neutropenia, thrombocytopenia, anorexia, nausea and vomiting, fatigue, and mucositis (p = 0.05-0.001). Our data demonstrate that GPS assessment is associated with poor clinical outcomes and severe chemotherapy-related toxicities in patients with metastatic breast cancer who have undergone chemotherapy, without any specific indication regarding the type of chemotherapy applied. © 2016 S. Karger AG, Basel.

BIOBEHAVIORAL PROGNOSTIC FACTORS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE: Results from the INSPIRE-II Trial

PubMed Central

Blumenthal, James A.; Smith, Patrick J.; Durheim, Michael; Mabe, Stephanie; Emery, Charles F.; Martinu, Tereza; Diaz, Philip T.; Babyak, Michael; Welty-Wolf, Karen; Palmer, Scott

2015-01-01

Objective To examine the prognostic value of select biobehavioral factors in patients with chronic obstructive pulmonary disease (COPD) in a secondary analysis of participants from the INSPIRE-II trial. Methods Three hundred twenty six outpatients with COPD underwent assessments of pulmonary function, physical activity, body mass index, inflammation, pulmonary symptoms, depression, and pulmonary quality of life, and were followed for up to 5.4 years for subsequent clinical events. The prognostic value of each biobehavioral factor, considered individually and combined, also was examined in the context of existing Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 risk stratification. Results Sixty-nine individuals experienced a hospitalization or died over a mean follow-up time period of 2.4 (interquartile range = 1.6) years. GOLD classification was associated with an increased risk of clinical events (HR = 2.72 [95% CI 1.63, 4.54], per stage); Six Minute Walk (HR = 0.50 [0.34, 0.73] per 500 feet), total steps (HR = 0.82 [0.71, 0.94] per 1,000 steps), hsC-reactive protein (HR = 1.44 [1.01, 2.06] per 4.5 mg/L), depression (HR = 1.12 [1.01, 1.25] per 4 points), and pulmonary quality of life (HR = 1.73 [1.14, 2.63] per 25 points) were each predictive over and above the GOLD assessment. However, only GOLD group and Six Minute Walk were predictive of all-cause mortality and COPD hospitalization when all biobehavioral variables were included together in a multivariable model. Conclusion Biobehavioral factors provide added prognostic information over and above measures of COPD severity in predicting adverse events in patients with COPD. PMID:26780299

The impact of herbal drug use on adverse drug reaction profiles of patients on antiretroviral therapy in zimbabwe.

PubMed

Mudzviti, Tinashe; Maponga, Charles C; Khoza, Star; Ma, Qing; Morse, Gene D

2012-01-01

Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076-0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292-0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles.

The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

PubMed Central

Mudzviti, Tinashe; Maponga, Charles C.; Khoza, Star; Ma, Qing; Morse, Gene D.

2012-01-01

Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076–0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292–0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles. PMID:22506106

Assessment of nitrogen ceilings for Dutch agricultural soils to avoid adverse environmental impacts.

PubMed

de Vries, W; Kros, H; Oenema, O; Erisman, J W

2001-11-09

In the Netherlands, high traffic density and intensive animal husbandry have led to high emissions of reactive nitrogen (N) into the environment. This leads to a series of environmental impacts, including: (1) nitrate (NO3) contamination of drinking water, (2) eutrophication of freshwater lakes, (3) acidification and biodiversity impacts on terrestrial ecosystems, (4) ozone and particle formation affecting human health, and (5) global climate change induced by emissions of N2O. Measures to control reactive N emissions were, up to now, directed towards those different environmental themes. Here we summarize the results of a study to analyse the agricultural N problem in the Netherlands in an integrated way, which means that all relevant aspects are taken into account simultaneously. A simple N balance model was developed, representing all crucial processes in the N chain, to calculate acceptable N inputs to the farm (so-called N ceiling) and to the soil surface (application in the field) by feed concentrates, organic manure, fertiliser, deposition, and N fixation. The N ceilings were calculated on the basis of critical limits for NO 3 concentrations in groundwater, N concentrations in surface water, and ammonia (NH3) emission targets related to the protection of biodiversity of natural areas. Results show that in most parts of the Netherlands, except the western and the northern part, the N ceilings are limited by NH 3 emissions, which are derived from critical N loads for nature areas, rather than limits for both ground- and surface water. On the national scale, the N ceiling ranges between 372 and 858 kton year(-1) depending on the choice of critical limits. The current N import is 848 kton year(-1). A decrease of nearly 60% is needed to reach the ceilings that are necessary to protect the environment against all adverse impacts of N pollution from agriculture.

The Prognostic Impact of the Evolution of RV Function in Idiopathic DCM.

PubMed

Merlo, Marco; Gobbo, Marco; Stolfo, Davide; Losurdo, Pasquale; Ramani, Federica; Barbati, Giulia; Pivetta, Alberto; Di Lenarda, Andrea; Anzini, Marco; Gigli, Marta; Pinamonti, Bruno; Sinagra, Gianfranco

2016-09-01

In this study, the authors analyzed the prognostic role of right ventricular systolic function (RVF) longitudinal trends in a large cohort of patients affected by dilated cardiomyopathy (DCM). RVF is a known prognostic predictor in DCM; however, whether RVF changes over time to better predict the long-term disease progression has not been investigated. From 1993 to 2008, we analyzed 512 patients with DCM (46 years of age [36 to 55 years of age], left ventricular ejection fraction 32% [25% to 41%]) with a potential follow-up of ≥72 months and available data at baseline and at least 1 pre-specified follow-up evaluation (i.e., 6, 24, 48, or 72 months). RV dysfunction was defined as RV fractional area change <35% at 2-dimensional echocardiography. The primary outcome measure was a composite of death or heart transplantation. At enrollment, 103 (20%) patients had RV dysfunction. During follow-up, 89 of them (86%, 17% of the overall cohort) normalized RVF at a median time of 6 months, whereas 38 of the remaining 409 patients with normal baseline RVF (9%; 7% of the overall population) exhibited a new-onset RV dysfunction (median time: 36 months). RVF normalization was significantly associated with subsequent left ventricular reverse remodeling that was observed at a median time of 24 months (odds ratio: 2.49; 95% confidence interval [CI]: 1.17 to 5.3; p = 0.018). At baseline multivariate analysis, RV dysfunction was independently associated with the primary outcome measure (hazard ratio: 1.71; 95% CI: 1.02 to 2.85; p = 0.0413). At time-dependent model, RVF revaluation over time maintained an independent predictive value (hazard ratio: 2.83; 95% CI: 1.57 to 5.11; p = 0.0006). Patients with DCM frequently present RV dysfunction at first evaluation. However, a complete RVF recovery is largely observed early after optimization of medical therapy and predates subsequent left ventricular reverse remodeling. Systematic revaluation of patients including RVF

Impact of medication reconciliation and review and counselling, on adverse drug events and healthcare resource use.

PubMed

Al-Hashar, Amna; Al-Zakwani, Ibrahim; Eriksson, Tommy; Sarakbi, Alaa; Al-Zadjali, Badriya; Al Mubaihsi, Saif; Al Zaabi, Mohammed

2018-05-12

Background Adverse drug events from preventable medication errors can result in patient morbidity and mortality, and in cost to the healthcare system. Medication reconciliation can improve communication and reduce medication errors at transitions in care. Objective Evaluate the impact of medication reconciliation and counselling intervention delivered by a pharmacist for medical patients on clinical outcomes 30 days after discharge. Setting Sultan Qaboos University Hospital, Muscat, Oman. Methods A randomized controlled study comparing standard care with an intervention delivered by a pharmacist and comprising medication reconciliation on admission and discharge, a medication review, a bedside medication counselling, and a take-home medication list. Medication discrepancies during hospitalization were identified and reconciled. Clinical outcomes were evaluated by reviewing electronic health records and telephone interviews. Main outcome measures Rates of preventable adverse drug events as primary outcome and healthcare resource utilization as secondary outcome at 30 days post discharge. Results A total of 587 patients were recruited (56 ± 17 years, 57% female); 286 randomized to intervention; 301 in the standard care group. In intervention arm, 74 (26%) patients had at least one discrepancy on admission and 100 (35%) on discharge. Rates of preventable adverse drug events were significantly lower in intervention arm compared to standard care arm (9.1 vs. 16%, p = 0.009). No significant difference was found in healthcare resource use. Conclusion The implementation of an intervention comprising medication reconciliation and counselling by a pharmacist has significantly reduced the rate of preventable ADEs 30 days post discharge, compared to the standard care. The effect of the intervention on healthcare resource use was insignificant. Pharmacists should be included in decentralized, patient-centred roles. The findings should be interpreted in the context

Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning.

PubMed

Tang, Weidong; Ruan, Feng; Chen, Qi; Chen, Suping; Shao, Xuebo; Gao, Jianbo; Zhang, Mao

2016-07-01

Acute organophosphorus pesticide poisoning (AOPP) is becoming a significant problem and a potential cause of human mortality because of the abuse of organophosphate compounds. This study aims to determine the independent prognostic factors of AOPP by using multivariate logistic regression analysis. The clinical data for 71 subjects with AOPP admitted to our hospital were retrospectively analyzed. This information included the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, admission blood cholinesterase levels, 6-h post-admission blood cholinesterase levels, cholinesterase activity, blood pH, and other factors. Univariate analysis and multivariate logistic regression analyses were conducted to identify all prognostic factors and independent prognostic factors, respectively. A receiver operating characteristic curve was plotted to analyze the testing power of independent prognostic factors. Twelve of 71 subjects died. Admission blood lactate levels, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, blood pH, and APACHE II scores were identified as prognostic factors for AOPP according to the univariate analysis, whereas only 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, and blood pH were independent prognostic factors identified by multivariate logistic regression analysis. The receiver operating characteristic analysis suggested that post-admission 6-h lactate clearance rates were of moderate diagnostic value. High 6-h post-admission blood lactate levels, low blood pH, and low post-admission 6-h lactate clearance rates were independent prognostic factors identified by multivariate logistic regression analysis. Copyright © 2016 by Daedalus Enterprises.

Prognostic value of left atrial function in systemic light-chain amyloidosis: a cardiac magnetic resonance study.

PubMed

Mohty, Dania; Boulogne, Cyrille; Magne, Julien; Varroud-Vial, Nicolas; Martin, Sylvain; Ettaif, Hind; Fadel, Bahaa M; Bridoux, Frank; Aboyans, Victor; Damy, Thibaud; Jaccard, Arnaud

2016-09-01

Cardiac involvement in systemic light-chain amyloidosis (AL) imparts an adverse impact on outcome. The left atrium (LA), by virtue of its anatomical location and muscular wall, is commonly affected by the amyloid process. Although LA infiltration by amyloid fibrils leads to a reduction in its pump function, the infiltration of the left ventricular (LV) myocardium results in diastolic dysfunction with subsequent increase in filling pressures and LA enlargement. Even though left atrial volume (LAV) is an independent prognostic marker in many cardiomyopathies, its value in amyloid heart disease remains to be determined. In addition, few data are available as to the prognostic value of LA function in systemic AL. Using cardiac magnetic resonance (CMR), the current study aims to assess the prognostic significance of the maximal LAV and total LA emptying fraction (LAEF) in patients with AL. Fifty-four consecutive patients (age 66 ± 10 years, 59% males) with confirmed systemic AL and mean LV ejection fraction of 60 ± 12% underwent CMR. As compared with patients with no or minimal cardiac involvement (Mayo Clinic [MC] stage I), those at moderate and high risk (MC stages II and III) had significantly larger indexed maximal LAV (36 ± 15 vs. 46 ± 13 vs. 52 ± 19 mL/m(2), P = 0.03) and indexed minimal LAV (20 ± 6 vs. 34 ± 11 vs. 44 ± 17 mL/m(2), P < 0.001), lower LAEF (42 ± 9 vs. 26 ± 13 vs. 16 ± 9%, P < 0.0001) but similar LVEF. Furthermore, myocardial late gadolinium enhancement (LGE) was more frequent and significantly associated with lower LAEF. LAEF was also significantly lower in symptomatic (NHYA ≥ II, 22 ± 14%) as compared with asymptomatic patients (NYHA class I, 33 ± 13%, P = 0.006). Two-year survival rate was lower in patients with LAEF ≤ 16% as compared with those with LAEF > 16% (37 ± 11 vs. 94 ± 4%, P = 0.001). In multivariate analysis, lower LAEF remained independently associated with a higher risk of 2-year mortality (HR = 1.08 per 1% decrease

Clinical review: insulin pump-associated adverse events in adults and children.

PubMed

Ross, P L; Milburn, J; Reith, D M; Wiltshire, E; Wheeler, B J

2015-12-01

Insulin pumps are a vital and rapidly developing tool in the treatment of type 1 diabetes mellitus in both adults and children. Many studies have highlighted outcomes and assessed their potential advantages, but much of the data on adverse outcomes are limited and often based on outdated technology. We aimed to review and summarize the available literature on insulin pump-associated adverse events in adults and children. A literature search was undertaken using PubMed, EMBASE, and the Cochrane library. Articles were then screened by title, followed by abstract, and full text as needed. A by-hand search of reference lists in identified papers was also utilised. All searches were limited to English language material, but no time limits were used. Current and past literature regarding insulin pump-associated adverse events is discussed, including potential metabolic and non-metabolic adverse events, in particular: pump malfunction; infusion set/site issues; and cutaneous problems. We show that even with modern technology, adverse events are common, occurring in over 40 % of users per year, with a minority, particularly in children, requiring hospital management. Hyperglycaemia and ketosis are now the most common consequences of adverse events and are usually associated with infusion set failure. This differs from older technology where infected infusion sites predominated. This timely review covers all potential insulin pump-associated adverse events, including their incidence, features, impacts, and contributory factors such as the pump user. The importance of ongoing anticipatory education and support for patients and families using this intensive insulin technology is highlighted, which if done well should improve the overall experience of pump therapy for users, and hopefully reduce the incidence and impact of severe adverse events.

New prognostic factors and scoring system for patients with skeletal metastasis.

PubMed

Katagiri, Hirohisa; Okada, Rieko; Takagi, Tatsuya; Takahashi, Mitsuru; Murata, Hideki; Harada, Hideyuki; Nishimura, Tetsuo; Asakura, Hirofumi; Ogawa, Hirofumi

2014-10-01

The aim of this study was to update a previous scoring system for patients with skeletal metastases, that was proposed by Katagiri et al. in 2005, by introducing a new factor (laboratory data) and analyzing a new patient cohort. Between January 2005 and January 2008, we treated 808 patients with symptomatic skeletal metastases. They were prospectively registered regardless of their treatments, and the last follow-up evaluation was performed in 2012. There were 441 male and 367 female patients with a median age of 64 years. Of these patients, 749 were treated nonsurgically while the remaining 59 underwent surgery for skeletal metastasis. A multivariate analysis was conducted using the Cox proportional hazards model. We identified six significant prognostic factors for survival, namely, the primary lesion, visceral or cerebral metastases, abnormal laboratory data, poor performance status, previous chemotherapy, and multiple skeletal metastases. The first three factors had a larger impact than the remaining three. The prognostic score was calculated by adding together all the scores for individual factors. With a prognostic score of ≥7, the survival rate was 27% at 6 months, and only 6% at 1 year. In contrast, patients with a prognostic score of ≤3 had a survival rate of 91% at 1 year, and 78% at 2 years. Comparing the revised system with the previous one, there was a significantly lower number of wrongly predicted patients using the revised system. This revised scoring system was able to predict the survival rates of patients with skeletal metastases more accurately than the previous system and may be useful for selecting an optimal treatment. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Free text adversity statements as part of a contextualised admissions process: a qualitative analysis.

PubMed

Owen, Lysa E; Anderson, Stephanie Ann; Dowell, Johnathan S

2018-04-02

Medical schools globally are encouraged to widen access and participation for students from less privileged backgrounds. Many strategies have been implemented to address this inequality, but much still needs to be done to ensure fair access for all. In the literature, adverse circumstances include financial issues, poor educational experience and lack of professional-status parents. In order to take account of adverse circumstances faced by applicants, The University of Dundee School of Medicine offers applicants the opportunity to report circumstances which may have resulted in disadvantage. Applicants do this by completing a free text statement, known as an 'adversity statement', in addition to the other application information. This study analysed adversity statements submitted by applicants during two admissions cycles. Analysis of content and theme was done to identify the information applicants wished to be taken into consideration, and what range of adverse circumstances individuals reported. This study used a qualitative approach with thematic analysis to categorise the adversity statements. The data was initially analysed to create a coding framework which was then applied to the whole data set. Each coded segment was then analysed for heterogeneity and homogeneity, segments merged into generated themes, or to create sub-themes. The data set comprised a total of 384 adversity statements. These showed a wide range of detail involving family, personal health, education and living circumstances. Some circumstances, such as geographical location, have been identified and explored in previous research, while others, such as long term health conditions, have had less attention in the literature. The degree of impact, the length of statement and degree of detail, demonstrated wide variation between submissions. This study adds to the debate on best practice in contextual admissions and raises awareness of the range of circumstances and impact applicants wish to

Recording Adverse Events Following Joint Arthroplasty: Financial Implications and Validation of an Adverse Event Assessment Form.

PubMed

Lee, Matthew J; Mohamed, Khalid M S; Kelly, John C; Galbraith, John G; Street, John; Lenehan, Brian J

2017-09-01

In Ireland, funding of joint arthroplasty procedures has moved to a pay-by-results national tariff system. Typically, adverse clinical events are recorded via retrospective chart-abstraction methods by administrative staff. Missed or undocumented events not only affect the quality of patient care but also may unrealistically skew budgetary decisions that impact fiscal viability of the service. Accurate recording confers clinical benefits and financial transparency. The aim of this study was to compare a prospectively implemented adverse events form with the current national retrospective chart-abstraction method in terms of pay-by-results financial implications. An adverse events form adapted from a similar validated model was used to prospectively record complications in 51 patients undergoing total hip or knee arthroplasties. Results were compared with the same cohort using an existing data abstraction method. Both data sets were coded in accordance with current standards for case funding. Overall, 114 events were recorded during the study through prospective charting of adverse events, compared with 15 events documented by customary method (a significant discrepancy). Wound drainage (15.8%) was the most common complication, followed by anemia (7.9%), lower respiratory tract infections (7.9%), and cardiac events (7%). A total of €61,956 ($67,778) in missed funding was calculated as a result. This pilot study demonstrates the ability to improve capture of adverse events through use of a well-designed assessment form. Proper perioperative data handling is a critical aspect of financial subsidies, enabling optimal allocation of funds. Copyright © 2017 Elsevier Inc. All rights reserved.

Distinguishing prognostic and predictive biomarkers: An information theoretic approach.

PubMed

Sechidis, Konstantinos; Papangelou, Konstantinos; Metcalfe, Paul D; Svensson, David; Weatherall, James; Brown, Gavin

2018-05-02

The identification of biomarkers to support decision-making is central to personalised medicine, in both clinical and research scenarios. The challenge can be seen in two halves: identifying predictive markers, which guide the development/use of tailored therapies; and identifying prognostic markers, which guide other aspects of care and clinical trial planning, i.e. prognostic markers can be considered as covariates for stratification. Mistakenly assuming a biomarker to be predictive, when it is in fact largely prognostic (and vice-versa) is highly undesirable, and can result in financial, ethical and personal consequences. We present a framework for data-driven ranking of biomarkers on their prognostic/predictive strength, using a novel information theoretic method. This approach provides a natural algebra to discuss and quantify the individual predictive and prognostic strength, in a self-consistent mathematical framework. Our contribution is a novel procedure, INFO+, which naturally distinguishes the prognostic vs predictive role of each biomarker and handles higher order interactions. In a comprehensive empirical evaluation INFO+ outperforms more complex methods, most notably when noise factors dominate, and biomarkers are likely to be falsely identified as predictive, when in fact they are just strongly prognostic. Furthermore, we show that our methods can be 1-3 orders of magnitude faster than competitors, making it useful for biomarker discovery in 'big data' scenarios. Finally, we apply our methods to identify predictive biomarkers on two real clinical trials, and introduce a new graphical representation that provides greater insight into the prognostic and predictive strength of each biomarker. R implementations of the suggested methods are available at https://github.com/sechidis. konstantinos.sechidis@manchester.ac.uk. Supplementary data are available at Bioinformatics online.

Family Adversity and Resilience Measures in Pediatric Acute Care Settings.

PubMed

O'Malley, Donna M; Randell, Kimberly A; Dowd, M Denise

2016-01-01

Adverse childhood experiences (ACEs) impact health across the life course. The purpose of this study was to identify caregiver ACEs, current adversity, and resilience in families seeking care in pediatric acute care settings. Study aims included identifying demographic characteristics, current adversities, and resilience measures associated with caregiver ACEs ≥4. A cross-sectional survey study design was used and a convenience sample (n = 470) recruited at emergency and urgent care settings of a large Midwest pediatric hospital system. Measures were self-reported. The original 10-item ACEs questionnaire measured caregiver past adversity. Current adversity was measured using the 10-item IHELP. The six-item Brief Resiliency Scale measured resilience, and WHO-5 Well-Being Index was used to measure depressive affect. Compared to participants with ACEs score of 0-3 participants with ACEs ≥4 were more likely to have multiple current adversities, increased risk of depression, and lower resilience. Caregivers using pediatric acute care settings carry a high burden of ACEs and current adversities. Caregiver ACEs are associated with current child experiences of adversity. Caregivers socioeconomic status and education level may not be an accurate indicator of a family's risks or needs. Pediatric acute care settings offer opportunities to access, intervene, and prevent childhood adversity. © 2016 Wiley Periodicals, Inc.

Comparative effectiveness of incorporating a hypothetical DCIS prognostic marker into breast cancer screening.

PubMed

Trentham-Dietz, Amy; Ergun, Mehmet Ali; Alagoz, Oguzhan; Stout, Natasha K; Gangnon, Ronald E; Hampton, John M; Dittus, Kim; James, Ted A; Vacek, Pamela M; Herschorn, Sally D; Burnside, Elizabeth S; Tosteson, Anna N A; Weaver, Donald L; Sprague, Brian L

2018-02-01

Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

Molecular Classification Substitutes for the Prognostic Variables Stage, Age, and MYCN Status in Neuroblastoma Risk Assessment.

PubMed

Rosswog, Carolina; Schmidt, Rene; Oberthuer, André; Juraeva, Dilafruz; Brors, Benedikt; Engesser, Anne; Kahlert, Yvonne; Volland, Ruth; Bartenhagen, Christoph; Simon, Thorsten; Berthold, Frank; Hero, Barbara; Faldum, Andreas; Fischer, Matthias

2017-12-01

Current risk stratification systems for neuroblastoma patients consider clinical, histopathological, and genetic variables, and additional prognostic markers have been proposed in recent years. We here sought to select highly informative covariates in a multistep strategy based on consecutive Cox regression models, resulting in a risk score that integrates hazard ratios of prognostic variables. A cohort of 695 neuroblastoma patients was divided into a discovery set (n=75) for multigene predictor generation, a training set (n=411) for risk score development, and a validation set (n=209). Relevant prognostic variables were identified by stepwise multivariable L1-penalized least absolute shrinkage and selection operator (LASSO) Cox regression, followed by backward selection in multivariable Cox regression, and then integrated into a novel risk score. The variables stage, age, MYCN status, and two multigene predictors, NB-th24 and NB-th44, were selected as independent prognostic markers by LASSO Cox regression analysis. Following backward selection, only the multigene predictors were retained in the final model. Integration of these classifiers in a risk scoring system distinguished three patient subgroups that differed substantially in their outcome. The scoring system discriminated patients with diverging outcome in the validation cohort (5-year event-free survival, 84.9±3.4 vs 63.6±14.5 vs 31.0±5.4; P<.001), and its prognostic value was validated by multivariable analysis. We here propose a translational strategy for developing risk assessment systems based on hazard ratios of relevant prognostic variables. Our final neuroblastoma risk score comprised two multigene predictors only, supporting the notion that molecular properties of the tumor cells strongly impact clinical courses of neuroblastoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Prognostic Impact and Predictors of Ejection Fraction Recovery in Patients With Alcoholic Cardiomyopathy.

PubMed

Amor-Salamanca, Almudena; Guzzo-Merello, Gonzalo; González-López, Esther; Domínguez, Fernando; Restrepo-Córdoba, Alejandra; Cobo-Marcos, Marta; Gómez-Bueno, Manuel; Segovia-Cubero, Javier; Alonso-Pulpón, Luis; García-Pavía, Pablo

2018-04-09

Recovery of left ventricular ejection fraction (LVEF) has been described in alcoholic cardiomyopathy (ACM) after a period of alcohol withdrawal. Nevertheless, the prognostic impact of LVEF recovery in ACM and its determinants have not been studied. We sought to define the role of LVEF improvement in the long-term outcome of ACM and to identify predictors of LVEF recovery in these patients. We evaluated 101 ACM patients during a median follow-up period of 82 months [interquartile range 36-134]. At latest follow-up, 42 patients (42%) showed substantial LVEF recovery defined as an absolute increase in LVEF ≥ 10% to a final value of ≥ 40%. Patients who recovered LVEF had better outcomes than patients who did not (heart transplant or cardiovascular death 1% vs 30%; P <.001). A QRS with <120ms (OR, 6.68; 95%CI, 2.30-19.41), beta-blocker therapy (OR, 3.01; 95%CI, 1.09-8.28), and the absence of diuretics (OR, 3.35; 95%CI, 1.08-10.42) predicted LVEF recovery in multivariate analysis. Although alcohol cessation did not predict LVEF recovery, none of the patients (n=6) who persisted with heavy alcohol consumption recovered LVEF. The rate of patients who recovered LVEF did not differ between abstainers and moderate drinkers (44% vs 45%; P=.9). The LVEF recovery is associated with an excellent prognosis in ACM. Beta-blocker treatment, QRS <120ms and absence of diuretics are independent predictors of LVEF recovery. LVEF recovery is similar in moderate drinkers and abstainers. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Prevalence and prognostic impact of electrocardiographic abnormalities in outpatients with extracardiac artery disease.

PubMed

Hysing, Per; Jonason, Tommy; Leppert, Jerzy; Hedberg, Pär

2017-11-24

Identifying cardiac disease in patients with extracardiac artery disease (ECAD) is essential for clinical decision-making. Electrocardiography (ECG) is an easily accessible tool to unmask subclinical cardiac disease and to risk stratify patient with or without manifest cardiovascular disease (CV). We aimed to examine the prevalence and prognostic impact of ECG changes in outpatients with ECAD. Outpatients with carotid or lower extremity artery disease (n = 435) and community-based controls (n = 397) underwent resting ECG. The patients were followed during a median of 4·8 years for CV events (hospitalization or death caused by ischaemic heart disease, cardiac arrest, heart failure, or stroke). ECG abnormalities were classified according to the Minnesota Code. Major (33% versus 15%, P<0·001) but not minor ECG abnormalities (23% versus 26%, P = 0·42) were significantly more common in patients versus controls. During the follow-up, 141 patients experienced CV events. Both major ECG abnormalities [hazard ratio (HR) 1·58, 95% confidence interval (CI) 1·11-2·25, P = 0·012] and any ECG abnormalities (HR 1·57, 95% CI 1·06-2·33, P = 0·024) were significantly associated with CV events after adjustment for potential risk factors. In conclusion, ECG abnormalities were common in these outpatients with ECAD. Major and any ECG abnormalities were independent predictors of CV events. Addition of easily accessible ECG information might be useful in risk stratification for such patients. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

A Discussion on Uncertainty Representation and Interpretation in Model-Based Prognostics Algorithms based on Kalman Filter Estimation Applied to Prognostics of Electronics Components

NASA Technical Reports Server (NTRS)

Celaya, Jose R.; Saxen, Abhinav; Goebel, Kai

2012-01-01

This article discusses several aspects of uncertainty representation and management for model-based prognostics methodologies based on our experience with Kalman Filters when applied to prognostics for electronics components. In particular, it explores the implications of modeling remaining useful life prediction as a stochastic process and how it relates to uncertainty representation, management, and the role of prognostics in decision-making. A distinction between the interpretations of estimated remaining useful life probability density function and the true remaining useful life probability density function is explained and a cautionary argument is provided against mixing interpretations for the two while considering prognostics in making critical decisions.

Increased risk of coronary heart disease among individuals reporting adverse impact of stress on their health: the Whitehall II prospective cohort study

PubMed Central

Nabi, Hermann; Kivimäki, Mika; Batty, G. David; Shipley, Martin J.; Britton, Annie; Brunner, Eric J.; Vahtera, Jussi; Lemogne, Cédric; Elbaz, Alexis; Singh-Manoux, Archana

2013-01-01

Aim Response to stress can vary greatly between individuals. However, it remains unknown whether perceived impact of stress on health is associated with adverse health outcomes. We examined whether individuals who report that stress adversely affects their health are at increased risk of coronary heart disease (CHD) compared with those who report that stress has no adverse health impact. Methods and results Analyses are based on 7268 men and women (mean age: 49.5 years, interquartile range: 11 years) from the British Whitehall II cohort study. Over 18 years of follow-up, there were 352 coronary deaths or first non-fatal myocardial infarction (MI) events. After adjustment for sociodemographic characteristics, participants who reported at baseline that stress has affected their health ‘a lot or extremely’ had a 2.12 times higher (95% CI 1.52–2.98) risk of coronary death or incident non-fatal MI when compared with those who reported no effect of stress on their health. This association was attenuated but remained statistically significant after adjustment for biological, behavioural, and other psychological risk factors including perceived stress levels, and measures of social support; fully adjusted hazard ratio: 1.49 (95% CI 1.01–2.22). Conclusions In this prospective cohort study, the perception that stress affects health, different from perceived stress levels, was associated with an increased risk of coronary heart disease. Randomized controlled trials are needed to determine whether disease risk can be reduced by increasing clinical attention to those who complain that stress greatly affects their health. PMID:23804585

Intelligent approach to prognostic enhancements of diagnostic systems

NASA Astrophysics Data System (ADS)

Vachtsevanos, George; Wang, Peng; Khiripet, Noppadon; Thakker, Ash; Galie, Thomas R.

2001-07-01

This paper introduces a novel methodology to prognostics based on a dynamic wavelet neural network construct and notions from the virtual sensor area. This research has been motivated and supported by the U.S. Navy's active interest in integrating advanced diagnostic and prognostic algorithms in existing Naval digital control and monitoring systems. A rudimentary diagnostic platform is assumed to be available providing timely information about incipient or impending failure conditions. We focus on the development of a prognostic algorithm capable of predicting accurately and reliably the remaining useful lifetime of a failing machine or component. The prognostic module consists of a virtual sensor and a dynamic wavelet neural network as the predictor. The virtual sensor employs process data to map real measurements into difficult to monitor fault quantities. The prognosticator uses a dynamic wavelet neural network as a nonlinear predictor. Means to manage uncertainty and performance metrics are suggested for comparison purposes. An interface to an available shipboard Integrated Condition Assessment System is described and applications to shipboard equipment are discussed. Typical results from pump failures are presented to illustrate the effectiveness of the methodology.

Risk factors and screening instruments to predict adverse outcomes for undifferentiated older emergency department patients: a systematic review and meta-analysis.

PubMed

Carpenter, Christopher R; Shelton, Erica; Fowler, Susan; Suffoletto, Brian; Platts-Mills, Timothy F; Rothman, Richard E; Hogan, Teresita M

2015-01-01

A significant proportion of geriatric patients experience suboptimal outcomes following episodes of emergency department (ED) care. Risk stratification screening instruments exist to distinguish vulnerable subsets, but their prognostic accuracy varies. This systematic review quantifies the prognostic accuracy of individual risk factors and ED-validated screening instruments to distinguish patients more or less likely to experience short-term adverse outcomes like unanticipated ED returns, hospital readmissions, functional decline, or death. A medical librarian and two emergency physicians conducted a medical literature search of PubMed, EMBASE, SCOPUS, CENTRAL, and ClinicalTrials.gov using numerous combinations of search terms, including emergency medical services, risk stratification, geriatric, and multiple related MeSH terms in hundreds of combinations. Two authors hand-searched relevant specialty society research abstracts. Two physicians independently reviewed all abstracts and used the revised Quality Assessment of Diagnostic Accuracy Studies instrument to assess individual study quality. When two or more qualitatively similar studies were identified, meta-analysis was conducted using Meta-DiSc software. Primary outcomes were sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for predictors of adverse outcomes at 1 to 12 months after the ED encounters. A hypothetical test-treatment threshold analysis was constructed based on the meta-analytic summary estimate of prognostic accuracy for one outcome. A total of 7,940 unique citations were identified yielding 34 studies for inclusion in this systematic review. Studies were significantly heterogeneous in terms of country, outcomes assessed, and the timing of post-ED outcome assessments. All studies occurred in ED settings and none used published clinical decision rule derivation methodology. Individual risk factors assessed included dementia, delirium, age, dependency

Prognostic significance of MRI findings in patients with myxoid-round cell liposarcoma.

PubMed

Tateishi, Ukihide; Hasegawa, Tadashi; Beppu, Yasuo; Kawai, Akira; Satake, Mitsuo; Moriyama, Noriyuki

2004-03-01

The aims of this study were to determine the prognostic significance of MRI findings in patients with myxoid-round cell liposarcomas and to clarify which MRI features best indicate tumors with adverse clinical behavior. The initial MRI studies of 36 pathologically confirmed myxoid-round cell liposarcomas were retrospectively reviewed, and observations from this review were correlated with the histopathologic features. MR images were evaluated by two radiologists with agreement by consensus, and both univariate and multivariate analyses were conducted to evaluate survival with a median clinical follow-up of 33 months (range, 9-276 months). Statistically significant MRI findings that favored a diagnosis of intermediate- or high-grade tumor were large tumor size (> 10 cm), deeply situated tumor, tumor possessing irregular contours, absence of lobulation, absence of thin septa, presence of thick septa, absence of tumor capsule, high-intensity signal pattern, pronounced enhancement, and globular or nodular enhancement. Of these MRI findings, thin septa (p < 0.05), a tumor capsule (p < 0.01), and pronounced enhancement (p < 0.01) were associated significantly, according to univariate analysis, with overall survival. Multivariate analysis indicated that pronounced enhancement was associated significantly with overall survival (p < 0.05). Contrast-enhanced MRI findings can indicate a good or adverse prognosis in patients with myxoid-round cell liposarcomas.

Population Trends of Central European Montane Birds Provide Evidence for Adverse Impacts of Climate Change on High-Altitude Species.

PubMed

Flousek, Jiří; Telenský, Tomáš; Hanzelka, Jan; Reif, Jiří

2015-01-01

Climate change is among the most important global threats to biodiversity and mountain areas are supposed to be under especially high pressure. Although recent modelling studies suggest considerable future range contractions of montane species accompanied with increased extinction risk, data allowing to test actual population consequences of the observed climate changes and identifying traits associated to their adverse impacts are very scarce. To fill this knowledge gap, we estimated long-term population trends of montane birds from 1984 to 2011 in a central European mountain range, the Giant Mountains (Krkonoše), where significant warming occurred over this period. We then related the population trends to several species' traits related to the climate change effects. We found that the species breeding in various habitats at higher altitudes had more negative trends than species breeding at lower altitudes. We also found that the species moved upwards as a response to warming climate, and these altitudinal range shifts were associated with more positive population trends at lower altitudes than at higher altitudes. Moreover, long-distance migrants declined more than residents or species migrating for shorter distances. Taken together, these results indicate that the climate change, besides other possible environmental changes, already influences populations of montane birds with particularly adverse impacts on high-altitude species such as water pipit (Anthus spinoletta). It is evident that the alpine species, predicted to undergo serious climatically induced range contractions due to warming climate in the future, already started moving along this trajectory.

Autonomous diagnostics and prognostics of signal and data distribution systems

NASA Astrophysics Data System (ADS)

Blemel, Kenneth G.

2001-07-01

Wiring is the nervous system of any complex system and is attached to or services nearly every subsystem. Damage to optical wiring systems can cause serious interruptions in communication, command and control systems. Electrical wiring faults and failures due to opens, shorts, and arcing probably result in adverse effects to the systems serviced by the wiring. Abnormalities in a system usually can be detected by monitoring some wiring parameter such as vibration, data activity or power consumption. This paper introduces the mapping of wiring to critical functions during system engineering to automatically define the Failure Modes Effects and Criticality Analysis. This mapping can be used to define the sensory processes needed to perform diagnostics during system engineering. This paper also explains the use of Operational Modes and Criticality Effects Analysis in the development of Sentient Wiring Systems as a means for diagnostic, prognostics and health management of wiring in aerospace and transportation systems.

A Model-Based Prognostics Approach Applied to Pneumatic Valves

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Goebel, Kai

2011-01-01

Within the area of systems health management, the task of prognostics centers on predicting when components will fail. Model-based prognostics exploits domain knowledge of the system, its components, and how they fail by casting the underlying physical phenomena in a physics-based model that is derived from first principles. Uncertainty cannot be avoided in prediction, therefore, algorithms are employed that help in managing these uncertainties. The particle filtering algorithm has become a popular choice for model-based prognostics due to its wide applicability, ease of implementation, and support for uncertainty management. We develop a general model-based prognostics methodology within a robust probabilistic framework using particle filters. As a case study, we consider a pneumatic valve from the Space Shuttle cryogenic refueling system. We develop a detailed physics-based model of the pneumatic valve, and perform comprehensive simulation experiments to illustrate our prognostics approach and evaluate its effectiveness and robustness. The approach is demonstrated using historical pneumatic valve data from the refueling system.

Impact of the International Prognostic Scoring System cytogenetic risk groups on the outcome of patients with primary myelodysplastic syndromes undergoing allogeneic stem cell transplantation from human leukocyte antigen-identical siblings: a retrospective analysis of the European Society for Blood and Marrow Transplantation-Chronic Malignancies Working Party.

PubMed

Onida, Francesco; Brand, Ronald; van Biezen, Anja; Schaap, Michel; von dem Borne, Peter A; Maertens, Johan; Beelen, Dietrich W; Carreras, Enric; Alessandrino, Emilio P; Volin, Liisa; Kuball, Jürgen H E; Figuera, Angela; Sierra, Jorge; Finke, Jürgen; Kröger, Nicolaus; de Witte, Theo

2014-10-01

Acquired chromosomal abnormalities are important prognostic factors in patients with myelodysplastic syndromes treated with supportive care and with disease-modifying therapeutic interventions, including allogeneic hematopoietic stem cell transplantation. To assess the prognostic impact of cytogenetic characteristics after hematopoietic stem cell transplantation accurately, we investigated a homogeneous group of 523 patients with primary myelodysplastic syndromes who have received stem cells from human leukocyte antigen-identical siblings. Overall survival at five years from transplantation in good, intermediate, and poor cytogenetic risk groups according to the International Prognostic Scoring System was 48%, 45% and 30%, respectively (P<0.01). Both the disease status (complete remission vs. not in complete remission) and the morphological classification at transplant in the untreated patients were significantly associated with probability of overall survival and relapse-free survival (P<0.01). The cytogenetic risk groups have no prognostic impact in untreated patients with refractory anemia ± ringed sideroblasts (P=0.90). However, combining the good and intermediate cytogenetic risk groups and comparing them to the poor-risk group showed within the other three disease-status-at-transplant groups a hazard ratio of 1.86 (95%CI: 1.41-2.45). In conclusion, this study shows that, in a large series of patients with primary myelodysplastic syndromes, poor-risk cytogenetics as defined by the standard International Prognostic Scoring System is associated with a relatively poor survival after allogeneic stem cell transplantation from human leukocyte antigen-identical siblings except in patients who are transplanted in refractory anemia/refractory anemia with ringed sideroblasts stage before progression to higher myelodysplastic syndrome stages. Copyright© Ferrata Storti Foundation.

Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer.

PubMed

Grönberg, Malin; Ahlin, Cecilia; Naeser, Ylva; Janson, Eva Tiensuu; Holmberg, Lars; Fjällskog, Marie-Louise

2017-01-01

Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer. Within a cohort of women with breast cancer with tumor size ≤ 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides. Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients-halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.

Latent Classes and Cumulative Impacts of Adverse Childhood Experiences.

PubMed

Barboza, Gia Elise

2018-05-01

Studies of adverse childhood experiences (ACEs) have gauged severity using a cumulative risk (CR) index. Few studies have focused on the nature of the context of adversity and their association with psychosocial outcomes. The objective of this study was to examine the patterning of ACEs and to explore the resultant patterns' association with HIV risk-taking, problem drinking, and depressive symptoms in adulthood. Latent class analysis (LCA) was used to identify homogeneous, mutually exclusive "classes" of 11 of the most commonly used ACEs. The LCA resulted in four high-risk profiles and one low-risk profile, which were labeled: (1) highly abusive and dysfunctional (3.3%; n = 1,983), (2) emotionally abusive alcoholic with parental conflict (6%, n = 3,303), (3) sexual abuse only (4.3%, n = 2,260), (4) emotionally abusive and alcoholic (30.3%, n = 17,460), and (5) normative, low risk (56.3%, n = 32,950). Compared to the low-risk class, each high-risk profile was differentially associated with adult psychosocial outcomes even when the conditional CR within that class was similar. The results further our understanding about the pattern of ACEs and the unique pathways to poor health. Implications for child welfare systems when dealing with individuals who have experienced multiple forms of early childhood maltreatment and/or household dysfunction are discussed.

Early Prognostication Markers in Cardiac Arrest Patients Treated with Hypothermia

PubMed Central

Karapetkova, Maria; Koenig, Matthew A.; Jia, Xiaofeng

2015-01-01

Background and purpose Established prognostication markers, such as clinical findings, electroencephalography (EEG), and biochemical markers, used by clinicians to predict neurologic outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. Methods MEDLINE and EMBASE were searched for evidence on the current standards for neurologic outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers, and multimodal approaches for prognostication were included and reviewed. Results While the prognostic accuracy of various tests has been questioned after TH, pupillary light reflexes and somatosensory evoked potentials (SSEP) are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 hours after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as MRI and CT, can identify functional and structural brain injury, but are not readily available at the patient’s bedside because of limited availability and high costs. Conclusions A multimodal algorithm composed of neurological examination, EEG-based quantitative testing, and SSEP, in conjunction with newer MRI sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed later than 72 hours after CA. PMID:26228521

Early prognostication markers in cardiac arrest patients treated with hypothermia.

PubMed

Karapetkova, M; Koenig, M A; Jia, X

2016-03-01

Established prognostication markers, such as clinical findings, electroencephalography (EEG) and biochemical markers, used by clinicians to predict neurological outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. MEDLINE and Embase were searched for evidence on the current standards for neurological outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers and multimodal approaches for prognostication are included and reviewed. Whilst the prognostic accuracy of various tests after TH has been questioned, pupillary light reflexes and somatosensory evoked potentials are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 h after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as magnetic resonance imaging and computed tomography, can identify functional and structural brain injury but are not readily available at the patient's bedside because of limited availability and high costs. A multimodal algorithm composed of neurological examination, EEG-based quantitative testing and somatosensory evoked potentials, in conjunction with newer magnetic resonance imaging sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed more than 72 h after CA. © 2015 EAN.

Impact of early psychosocial factors (childhood socioeconomic factors and adversities) on future risk of type 2 diabetes, metabolic disturbances and obesity: a systematic review

PubMed Central

2010-01-01

Background Psychological factors and socioeconomic status (SES) have a notable impact on health disparities, including type 2 diabetes risk. However, the link between childhood psychosocial factors, such as childhood adversities or parental SES, and metabolic disturbances is less well established. In addition, the lifetime perspective including adult socioeconomic factors remains of further interest. We carried out a systematic review with the main question if there is evidence in population- or community-based studies that childhood adversities (like neglect, traumata and deprivation) have considerable impact on type 2 diabetes incidence and other metabolic disturbances. Also, parental SES was included in the search as risk factor for both, diabetes and adverse childhood experiences. Finally, we assumed that obesity might be a mediator for the association of childhood adversities with diabetes incidence. Therefore, we carried out a second review on obesity, applying a similar search strategy. Methods Two systematic reviews were carried out. Longitudinal, population- or community-based studies were included if they contained data on psychosocial factors in childhood and either diabetes incidence or obesity risk. Results We included ten studies comprising a total of 200,381 individuals. Eight out of ten studies indicated that low parental status was associated with type 2 diabetes incidence or the development of metabolic abnormalities. Adjustment for adult SES and obesity tended to attenuate the childhood SES-attributable risk but the association remained. For obesity, eleven studies were included with a total sample size of 70,420 participants. Four out of eleven studies observed an independent association of low childhood SES on the risk for overweight and obesity later in life. Conclusions Taken together, there is evidence that childhood SES is associated with type 2 diabetes and obesity in later life. The database on the role of psychological factors such as

Localized primary gastrointestinal diffuse large B cell lymphoma received a surgical approach: an analysis of prognostic factors and comparison of staging systems in 101 patients from a single institution.

PubMed

Zhang, Shengting; Wang, Li; Yu, Dong; Shen, Yang; Cheng, Shu; Zhang, Li; Qian, Ying; Shen, Zhixiang; Li, Qinyu; Zhao, Weili

2015-08-15

Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma and is a heterogeneous group of disease. Prognostic characterization of individual patients is an essential prerequisite for a proper risk-based therapeutic choice. Clinical and pathological prognostic factors were identified, and predictive value of four previously described prognostic systems were assessed in 101 primary gastrointestinal DLBCL (PG-DLBCL) patients with localized disease, including Ann Arbor staging with Musshoff modification, International Prognostic Index (IPI), Lugano classification, and Paris staging system. Univariate factors correlated with inferior survival time were clinical parameters [age>60 years old, multiple extranodal/gastrointestinal involvement, elevated serum lactate dehydrogenase and β2-microglobulin, and decreased serum albumin], as well as pathological parameters (invasion depth beyond serosa, involvement of regional lymph node or adjacent tissue, Ki-67 index, and Bcl-2 expression). Major independent variables of adverse outcome indicated by multivariate analysis were multiple gastrointestinal involvement. In patients unfit for Rituximab but received surgery, radical surgery significantly prolonged the survival time, comparing with alleviative surgery. Addition of Rituximab could overcome the negative prognostic effect of alleviative surgery. Among the four prognostic systems, IPI and Lugano classification clearly separated patients into different risk groups. IPI was able to further stratify the early-stage patients of Lugano classification into groups with distinct prognosis. Radical surgery might be proposed for the patients unfit for Rituximab treatment, and a combination of clinical and pathological staging systems was more helpful to predict the disease outcome of PG-DLBCL patients.

Childhood adversity profiles and adult psychopathology in a representative Northern Ireland study.

PubMed

McLafferty, Margaret; Armour, Cherie; McKenna, Aine; O'Neill, Siobhan; Murphy, Sam; Bunting, Brendan

2015-10-01

Childhood adversities are key aetiological factors in the onset and persistence of psychopathology. The aims of this study were to identify childhood adversity profiles, and investigate the relationship between the adversity classes and psychopathology in Northern Ireland. The study utilized data from the Northern Ireland Study of Health and Stress, an epidemiological survey (N=1986), which used the CIDI to examine mental health disorders and associated risk factors. Latent Class Analysis revealed 3 distinct typologies; a low risk class (n=1709; 86%), a poly-adversity class (n=122; 6.1%), and an economic adversity class (n=155; 7.8%). Logistic Regression models revealed that individuals in the economic adversity class had a heightened risk of anxiety and substance disorders, with individuals in the poly-adversity class more likely to have a range of mental health problems and suicidality. The findings indicate the importance of considering the impact of co-occurring childhood adversities when planning treatment, prevention, and intervention programmes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Left ventricular energy model predicts adverse events in women with suspected myocardial ischemia: results from the NHLBI-sponsored women’s ischemia syndrome evaluation (WISE) study

PubMed Central

Weinberg, Nicole; Pohost, Gerald M.; Bairey Merz, C. Noel; Shaw, Leslee J.; Sopko, George; Fuisz, Anthon; Rogers, William J.; Walsh, Edward G.; Johnson, B. Delia; Sharaf, Barry L.; Pepine, Carl J.; Mankad, Sunil; Reis, Steven E.; Rayarao, Geetha; Vido, Diane A.; Bittner, Vera; Tauxe, Lindsey; Olson, Marian B.; Kelsey, Sheryl F.; Biederman, Robert WW

2013-01-01

Objectives To assess the prognostic value of a left ventricular energy-model in women with suspected myocardial ischemia. Background The prognostic value of internal energy utilization (IEU) of the left ventricle in women with suspected myocardial ischemia is unknown. Methods Women [n=227, mean age 59±12 years (range, 31-86 years)], with symptoms of myocardial ischemia, underwent myocardial perfusion imaging (MPI) assessment for regional perfusion defects along with measurement of ventricular volumes separately by gated Single Photon Emission Computed Tomography (SPECT) (n=207) and magnetic resonance imaging (MRI) (n=203). During follow-up (40±17 months), time to first major adverse cardiovascular event (MACE, death, myocardial infarction or hospitalization for congestive heart failure) was analyzed using MRI and gated SPECT variables. Results Adverse events occurred in 31 (14%). Multivariable Cox models were formed for each modality: IEU and wall thickness by MRI (Chi-squared 34, P<0.005) and IEU and systolic blood pressure by gated SEPCT (Chi-squared 34, P<0.005). The models remained predictive after adjustment for age, disease history and Framingham risk score. For each Cox model, patients were categorized as high-risk if the model hazard was positive and not high-risk otherwise. Kaplan-Meier analysis of time to MACE was performed for high-risk vs. not high-risk for MR (log rank 25.3, P<0.001) and gated SEPCT (log rank 18.2, P<0.001) models. Conclusions Among women with suspected myocardial ischemia a high internal energy utilization has higher prognostic value than either a low EF or the presence of a myocardial perfusion defect assessed using two independent modalities of MR or gated SPECT. PMID:24015377

Diagnostic and Prognostic Models for Generator Step-Up Transformers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vivek Agarwal; Nancy J. Lybeck; Binh T. Pham

In 2014, the online monitoring (OLM) of active components project under the Light Water Reactor Sustainability program at Idaho National Laboratory (INL) focused on diagnostic and prognostic capabilities for generator step-up transformers. INL worked with subject matter experts from the Electric Power Research Institute (EPRI) to augment and revise the GSU fault signatures previously implemented in the Electric Power Research Institute’s (EPRI’s) Fleet-Wide Prognostic and Health Management (FW-PHM) Suite software. Two prognostic models were identified and implemented for GSUs in the FW-PHM Suite software. INL and EPRI demonstrated the use of prognostic capabilities for GSUs. The complete set of faultmore » signatures developed for GSUs in the Asset Fault Signature Database of the FW-PHM Suite for GSUs is presented in this report. Two prognostic models are described for paper insulation: the Chendong model for degree of polymerization, and an IEEE model that uses a loading profile to calculates life consumption based on hot spot winding temperatures. Both models are life consumption models, which are examples of type II prognostic models. Use of the models in the FW-PHM Suite was successfully demonstrated at the 2014 August Utility Working Group Meeting, Idaho Falls, Idaho, to representatives from different utilities, EPRI, and the Halden Research Project.« less

Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer.

PubMed

Polat, Bülent; Kaiser, Philipp; Wohlleben, Gisela; Gehrke, Thomas; Scherzad, Agmal; Scheich, Matthias; Malzahn, Uwe; Fischer, Thomas; Vordermark, Dirk; Flentje, Michael

2017-01-03

In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery. Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFβ1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2). A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFβ1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFβ1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003). Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFβ1 had prognostic impact.

[PROGNOSTIC MODELS IN MODERN MANAGEMENT OF VULVAR CANCER].

PubMed

Tsvetkov, Ch; Gorchev, G; Tomov, S; Nikolova, M; Genchev, G

2016-01-01

The aim of the research was to evaluate and analyse prognosis and prognostic factors in patients with squamous cell vulvar carcinoma after primary surgery with individual approach applied during the course of treatment. In the period between January 2000 and July 2010, 113 patients with squamous cell carcinoma of the vulva were diagnosed and operated on at Gynecologic Oncology Clinic of Medical University, Pleven. All the patients were monitored at the same clinic. Individual approach was applied to each patient and whenever it was possible, more conservative operative techniques were applied. The probable clinicopathological characteristics influencing the overall survival and recurrence free survival were analyzed. Univariate statistical analysis and Cox regression analysis were made in order to evaluate the characteristics, which were statistically significant for overall survival and survival without recurrence. A multivariate logistic regression analysis (Forward Wald procedure) was applied to evaluate the combined influence of the significant factors. While performing the multivariate analysis, the synergic effect of the independent prognostic factors of both kinds of survivals was also evaluated. Approaching individually each patient, we applied the following operative techniques: 1. Deep total radical vulvectomy with separate incisions for lymph dissection (LD) or without dissection--68 (60.18 %) patients. 2. En-bloc vulvectomy with bilateral LD without vulva reconstruction--10 (8.85%) 3. Modified radical vulvactomy (hemivulvectomy, patial vulvactomy)--25 (22.02%). 4. wide-local excision--3 (2.65%). 5. Simple (total /partial) vulvectomy--5 (4.43%) patients. 6. En-bloc resection with reconstruction--2 (1.77%) After a thorough analysis of the overall survival and recurrence free survival, we made the conclusion that the relapse occurrence and clinical stage of FIGO were independent prognostic factors for overall survival and the independent prognostic factors

Impact of prognostic factors for postmastectomy radiation therapy of breast cancer patients

NASA Astrophysics Data System (ADS)

Simonov, K. A.; Startseva, Zh. A.; Slonimskaya, E. M.; Velikaya, V. V.

2017-09-01

The study included 196 breast cancer patients with stages T1-3N0-3M0. The comprehensive therapy for breast cancer included surgical operation, chemotherapy, and radiotherapy. Multivariate analysis showed that multifocality growth of tumor (p = 0.004), high grade III (p = 0.008), two metastatic lymph nodes (p = 0.02) were associated with an increased risk of regional node failure in the patients with one to three positive lymph nodes. The prognostic models describing the probability of local recurrences of breast cancer were developed for individualization of the radiation therapy tactics. Postmastectomy radiation therapy in the patients with high-risk breast cancer treated with modified radical mastectomy improves locoregional control, breast cancer-specific survival, does not increase late toxicity.

Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer

PubMed Central

Enzinger, Andrea C.; Zhang, Baohui; Schrag, Deborah; Prigerson, Holly G.

2015-01-01

Purpose To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer. Patients and Methods This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences. Results Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses. Conclusion Prognostic disclosures are associated with more realistic

Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer.

PubMed

Enzinger, Andrea C; Zhang, Baohui; Schrag, Deborah; Prigerson, Holly G

2015-11-10

To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer. This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences. Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses. Prognostic disclosures are associated with more realistic patient expectations of LE, without decrements to

Analyzing risks of adverse pregnancy outcomes.

PubMed

Kramer, Michael S; Zhang, Xun; Platt, Robert W

2014-02-01

Approaches for analyzing the risks of adverse pregnancy outcomes have been the source of much debate and many publications. Much of the problem, in our view, is the conflation of time at risk with gestational age at birth (or birth weight, a proxy for gestational age). We consider the causal questions underlying such analyses with the help of a generic directed acyclic graph. We discuss competing risks and populations at risk in the context of appropriate numerators and denominators, respectively. We summarize 3 different approaches to quantifying risks with respect to gestational age, each of which addresses a distinct etiological or prognostic question (i.e., cumulative risk, prospective risk, or instantaneous risk (hazard)) and suggest the appropriate denominators for each. We show how the gestational age-specific risk of perinatal death (PND) can be decomposed as the product of the gestational age-specific risk of birth and the risk of PND conditional on birth at a given gestational age. Finally, we demonstrate how failure to consider the first of these 2 risks leads to selection bias. This selection bias creates the well-known crossover paradox, thus obviating the need to posit common causes of early birth and PND other than the study exposure.

Fear of knowledge: Clinical hypotheses in diagnostic and prognostic reasoning.

PubMed

Chiffi, Daniele; Zanotti, Renzo

2017-10-01

Patients are interested in receiving accurate diagnostic and prognostic information. Models and reasoning about diagnoses have been extensively investigated from a foundational perspective; however, for all its importance, prognosis has yet to receive a comparable degree of philosophical and methodological attention, and this may be due to the difficulties inherent in accurate prognostics. In the light of these considerations, we discuss a considerable body of critical thinking on the topic of prognostication and its strict relations with diagnostic reasoning, pointing out the distinction between nosographic and pathophysiological types of diagnosis and prognosis, underlying the importance of the explication and explanation processes. We then distinguish between various forms of hypothetical reasoning applied to reach diagnostic and prognostic judgments, comparing them with specific forms of abductive reasoning. The main thesis is that creative abduction regarding clinical hypotheses in diagnostic process is very unlikely to occur, whereas this seems to be often the case for prognostic judgments. The reasons behind this distinction are due to the different types of uncertainty involved in diagnostic and prognostic judgments. © 2016 John Wiley & Sons, Ltd.

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan

PubMed Central

Lee, Cheng-Chia; Wu, Patricia W.; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei

2017-01-01

Background Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. Methods This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Results Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. Conclusions The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients. PMID:28301536

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan.

PubMed

Lu, Yueh-An; Tu, Kun-Hua; Lee, Cheng-Chia; Wu, Patricia W; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei; Chu, Pao-Hsien

2017-01-01

Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients.

Prognostics

NASA Technical Reports Server (NTRS)

Goebel, Kai; Vachtsevanos, George; Orchard, Marcos E.

2013-01-01

Knowledge discovery, statistical learning, and more specifically an understanding of the system evolution in time when it undergoes undesirable fault conditions, are critical for an adequate implementation of successful prognostic systems. Prognosis may be understood as the generation of long-term predictions describing the evolution in time of a particular signal of interest or fault indicator, with the purpose of estimating the remaining useful life (RUL) of a failing component/subsystem. Predictions are made using a thorough understanding of the underlying processes and factor in the anticipated future usage.

The correlation of extranodal invasion with other prognostic parameters in lymph node positive breast cancer.

PubMed

Altinyollar, Hüseyin; Berberoğlu, Uğur; Gülben, Kaptan; Irkin, Fikret

2007-06-01

The presence of extranodal invasion (ENI) in the metastatic lymph nodes is reported to increase the risk of locoregional recurrence while shortening disease-free and overall survival in patients with breast cancer. In this study the relationship between ENI and other prognostic parameters and survival is investigated. Of 650 patients with breast cancer who were treated in Ankara Oncology Teaching and Research Hospital from 1996 to 2003, 368 (56.6%) had lymph node metastasis. The patients with axillary metastasis were separated into two groups as with and without invasion to lymph node capsule and the surrounding adipose tissue. Clinicopathologic features were analyzed by univariate and multivariate logistic regression. Of 368 patients with axillary metastasis, 135 (36.7%) had ENI. Based on multivariate analysis; the number of metastatic lymph nodes, lymphatic invasion, and tumor necrosis were found to be related with ENI. In the group with ENI, 5-year overall survival rate was 74.8%, compared to 82.3% for patients without ENI which was significantly lower (P = 0.04). In lymph node positive breast cancer with presence of ENI, adverse prognostic parameters are more frequently encountered and has a worse overall survival compared to group without ENI. (c) 2007 Wiley-Liss, Inc.

Commentary: Childhood Exposure to Environmental Adversity and the Well-Being of People with Intellectual Disabilities

ERIC Educational Resources Information Center

Emerson, E.

2013-01-01

People with intellectual disabilities have poorer health than their non-disabled peers. They are also more likely to be exposed to a wide range of environmental adversities in childhood. Research undertaken in the general population has demonstrated that exposure to environmental adversity in childhood can have an adverse impact on health and…

Impact of Extended-Duration Shifts on Medical Errors, Adverse Events, and Attentional Failures

PubMed Central

Barger, Laura K; Ayas, Najib T; Cade, Brian E; Cronin, John W; Rosner, Bernard; Speizer, Frank E; Czeisler, Charles A

2006-01-01

Background A recent randomized controlled trial in critical-care units revealed that the elimination of extended-duration work shifts (≥24 h) reduces the rates of significant medical errors and polysomnographically recorded attentional failures. This raised the concern that the extended-duration shifts commonly worked by interns may contribute to the risk of medical errors being made, and perhaps to the risk of adverse events more generally. Our current study assessed whether extended-duration shifts worked by interns are associated with significant medical errors, adverse events, and attentional failures in a diverse population of interns across the United States. Methods and Findings We conducted a Web-based survey, across the United States, in which 2,737 residents in their first postgraduate year (interns) completed 17,003 monthly reports. The association between the number of extended-duration shifts worked in the month and the reporting of significant medical errors, preventable adverse events, and attentional failures was assessed using a case-crossover analysis in which each intern acted as his/her own control. Compared to months in which no extended-duration shifts were worked, during months in which between one and four extended-duration shifts and five or more extended-duration shifts were worked, the odds ratios of reporting at least one fatigue-related significant medical error were 3.5 (95% confidence interval [CI], 3.3–3.7) and 7.5 (95% CI, 7.2–7.8), respectively. The respective odds ratios for fatigue-related preventable adverse events, 8.7 (95% CI, 3.4–22) and 7.0 (95% CI, 4.3–11), were also increased. Interns working five or more extended-duration shifts per month reported more attentional failures during lectures, rounds, and clinical activities, including surgery and reported 300% more fatigue-related preventable adverse events resulting in a fatality. Conclusions In our survey, extended-duration work shifts were associated with an

Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma.

PubMed

Lee, Yi-Ying; Chao, Tung-Bo; Sheu, Ming-Jen; Tian, Yu-Feng; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Lin, Ching-Yih; Li, Chien-Feng

2016-01-01

Background : Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting enzyme involving in the production of γ-aminobutyric acid (GABA), exists in the GABAergic neurons in the central nervous system (CNS). Little is known about the relevance of GAD1 to nasopharyngeal carcinoma (NPC). Through data mining on a data set derived from a published transcriptome database, this study first identified GAD1 as a differentially upregulated gene in NPC. We aimed to evaluate GAD1 expression and its prognostic effect on patients with early and locoregionally advanced NPC. Methods : We evaluated GAD1 immunohistochemistry and performed an H-score analysis on biopsy specimens from 124 patients with nonmetastasized NPC receiving treatment. GAD1 overexpression was defined as an H score higher than the median value. The findings of such an analysis are correlated with clinicopathological behaviors and survival rates, namely disease-specific survival (DSS), distant-metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) rates. Results : GAD1 overexpression was significantly associated with an increase in the primary tumor status ( p < 0.001) and American Joint Committee on Cancer (AJCC) stages III-IV ( p = 0.002) and was a univariate predictor of adverse outcomes of DSS ( p = 0.002), DMeFS ( p < 0.0001), and LRFS ( p = 0.001). In the multivariate comparison, in addition to advanced AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of short DSS ( p = 0.004, hazard ratio = 2.234), DMeFS ( p < 0.001, hazard ratio = 4.218), and LRFS ( p = 0.013, hazard ratio = 2.441) rates. Conclusions : Our data reveal that GAD1 overexpression was correlated with advanced disease status and may thus be a critical prognostic indicator of poor outcomes in NPC and a potential therapeutic target to facilitate the development of effective treatment modalities.

Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis.

PubMed

Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro; Romero, Alberto Omar; Machiavelli, Mario Raúl; Pérez, Juan Eduardo; Leone, Julieta; Leone, José Pablo

2017-02-01

To analyze the prognostic influence of metastatic pattern (MP) compared with other biologic and clinical factors in stage IV breast cancer at initial diagnosis (BCID) and evaluate factors associated with specific sites of metastases (SSM). We evaluated women with stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2013. MP was categorized as bone-only, visceral, bone and visceral (BV), and other. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with SSM. We included 9143 patients. Bone represented 37.5% of patients, visceral 21.9%, BV 28.8%, and other 11.9%. Median OS by MP was as follows: bone 38 months, visceral 21 months, BV 19 months, and other 33 months (P < 0.0001). Univariate analysis showed that higher number of metastatic sites had worse prognosis. In multivariate analysis, older age (hazard ratio 1.9), black race (hazard ratio 1.17), grade 3/4 tumors (hazard ratio 1.6), triple-negative (hazard ratio 2.24), BV MP (hazard ratio 2.07), and unmarried patients (hazard ratio 1.25) had significantly shorter OS. As compared with HR+/HER2- tumors, triple-negative and HR-/HER2+ had higher odds of brain, liver, lung, and other metastases. HR+/HER2+ had higher odds of liver metastases. All three subtypes had lower odds of bone metastases. There were substantial differences in OS according to MP. Tumor subtypes have a clear influence among other factors on SSM. We identified several prognostic factors that could guide therapy selection in treatment naïve patients.

Early life adversity and telomere length: a meta-analysis.

PubMed

Ridout, K K; Levandowski, M; Ridout, S J; Gantz, L; Goonan, K; Palermo, D; Price, L H; Tyrka, A R

2018-04-01

Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.

The prognostic value of undetectable highly sensitive cardiac troponin I in patients with acute pulmonary embolism.

PubMed

Hakemi, Emad U; Alyousef, Tareq; Dang, Geetanjali; Hakmei, Jalal; Doukky, Rami

2015-03-01

Elevated cardiac troponin levels have been shown to be associated with adverse outcomes in patients with acute pulmonary embolism (PE). However, few data address the management implications of undetectable cardiac troponin I (cTnI) using a highly sensitive assay. We hypothesized that undetectable cTnI predicts very low in-hospital adverse event rates. In a retrospective cohort study, we classified patients with confirmed acute PE according to cTnI detectability into cTnI+ (≥ 0.012 ng/mL) and cTnI- (< 0.012 ng/mL) groups. The Pulmonary Embolism Severity Index (PESI) was used for clinical risk determination. The primary outcome was a composite of hard events defined as in-hospital death, CPR, or thrombolytic therapy. The secondary outcome was a composite of soft events defined as ICU admission or inferior vena cava filter placement. Among 298 consecutive patients with confirmed acute PE, 161 (55%) were cTnI+ and 137 (45%) cTnI-. No deaths occurred in the cTnI- group vs nine (6%) in the cTnI+ group (P = .004). No hard events were observed in the cTnI- group vs 15 (9%) in the cTnI+ group (P < .001). Soft events were observed at a lower rate in the cTnI- group (21[15%] vs 69 [43%], P < .001). Patients in the cTnI- group had a higher survival rate free of hard (P = .001) or soft (P < .001) events, irrespective of clinical risk. Furthermore, cTnI provided incremental prognostic value beyond clinical, ECG, and imaging data (P < .001). Highly sensitive cTnI assay provides an excellent prognostic negative predictive value; thus, it plays a role in identifying candidates for out-of-hospital treatment of acute PE.

Prognostic impact of sarcopenia in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

PubMed

Go, Se-Il; Park, Mi Jung; Song, Haa-Na; Kim, Hoon-Gu; Kang, Myoung Hee; Lee, Hyang Rae; Kim, Yire; Kim, Rock Bum; Lee, Soon Il; Lee, Gyeong-Won

2016-12-01

Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in patients with diffuse large B-cell lymphoma (DLBCL). In total, 187 consecutive patients with DLBCL treated with induction rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy were reviewed. Sarcopenia was defined as the lowest sex-specific quartile of the skeletal muscle index, calculated by dividing the pectoralis muscle area by the height. Clinical outcomes were compared between the sarcopenic and non-sarcopenic groups. A nomogram was constructed from the Cox regression model for overall survival (OS). Treatment-related mortality (21.7 vs. 5.0%, P  = 0.002) and early discontinuation of treatment (32.6 vs. 14.9%, P  = 0.008) were more common in the sarcopenic group than in the non-sarcopenic group. The 5 year progression-free survival (PFS) rates were 35.3% in the sarcopenic group and 65.8% in the non-sarcopenic group ( P  < 0.001). The 5 year OS rates were 37.3% in the sarcopenic group and 68.1% in the non-sarcopenic group ( P  < 0.001). Sarcopenia and the five variables of the International Prognostic Index (IPI) were independent prognostic factors in a multivariate analysis for PFS and OS and were used to construct the nomogram. The calibration plot showed good agreement between the nomogram predictions and actual observations. The c index of the nomogram (0.80) was higher than those of other prognostic indices (IPI, 0.77, P  = 0.009; revised-IPI, 0.74, P  < 0.001; National Comprehensive Cancer Network-IPI, 0.77, P  = 0.062). Sarcopenia is associated with intolerance to standard R-CHOP chemotherapy as well as a poor prognosis. Moreover, sarcopenia itself can be included in prognostic models in DLBCL.

At convenience and systematic random sampling: effects on the prognostic value of nuclear area assessments in breast cancer patients.

PubMed

Jannink, I; Bennen, J N; Blaauw, J; van Diest, P J; Baak, J P

1995-01-01

This study compares the influence of two different nuclear sampling methods on the prognostic value of assessments of mean and standard deviation of nuclear area (MNA, SDNA) in 191 consecutive invasive breast cancer patients with long term follow up. The first sampling method used was 'at convenience' sampling (ACS); the second, systematic random sampling (SRS). Both sampling methods were tested with a sample size of 50 nuclei (ACS-50 and SRS-50). To determine whether, besides the sampling methods, sample size had impact on prognostic value as well, the SRS method was also tested using a sample size of 100 nuclei (SRS-100). SDNA values were systematically lower for ACS, obviously due to (unconsciously) not including small and large nuclei. Testing prognostic value of a series of cut off points, MNA and SDNA values assessed by the SRS method were prognostically significantly stronger than the values obtained by the ACS method. This was confirmed in Cox regression analysis. For the MNA, the Mantel-Cox p-values from SRS-50 and SRS-100 measurements were not significantly different. However, for the SDNA, SRS-100 yielded significantly lower p-values than SRS-50. In conclusion, compared with the 'at convenience' nuclear sampling method, systematic random sampling of nuclei is not only superior with respect to reproducibility of results, but also provides a better prognostic value in patients with invasive breast cancer.

Independent Prognostic Value of Serum Markers in Diffuse Large B-Cell Lymphoma in the Era of the NCCN-IPI.

PubMed

Melchardt, Thomas; Troppan, Katharina; Weiss, Lukas; Hufnagl, Clemens; Neureiter, Daniel; Tränkenschuh, Wolfgang; Schlick, Konstantin; Huemer, Florian; Deutsch, Alexander; Neumeister, Peter; Greil, Richard; Pichler, Martin; Egle, Alexander

2015-12-01

Several serum parameters have been evaluated for adding prognostic value to clinical scoring systems in diffuse large B-cell lymphoma (DLBCL), but none of the reports used multivariate testing of more than one parameter at a time. The goal of this study was to validate widely available serum parameters for their independent prognostic impact in the era of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score to determine which were the most useful. This retrospective bicenter analysis includes 515 unselected patients with DLBCL who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and January 2014. Anemia, high C-reactive protein, and high bilirubin levels had an independent prognostic value for survival in multivariate analyses in addition to the NCCN-IPI, whereas neutrophil-to-lymphocyte ratio, high gamma-glutamyl transferase levels, and platelets-to-lymphocyte ratio did not. In our cohort, we describe the most promising markers to improve the NCCN-IPI. Anemia and high C-reactive protein levels retain their power in multivariate testing even in the era of the NCCN-IPI. The negative role of high bilirubin levels may be associated as a marker of liver function. Further studies are warranted to incorporate these markers into prognostic models and define their role opposite novel molecular markers. Copyright © 2015 by the National Comprehensive Cancer Network.

Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study

PubMed Central

2010-01-01

Background We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection. Methods Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5%) satisfied the selection criteria. Results Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2%) which was followed by nasal cavity (n = 30, 23.3%), genitourinary (n = 21, 16.3%), oral cavity (n = 14, 10.9%), upper gastrointestinal tract (n = 6, 4.7%) and maxillary sinus (n = 5, 3.9%) in the order of frequency. With the median 64.5 (range 4.3-213.0) months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5) for all patients, and 34.6 (95% CI 24.5-44.7) months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin), and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04). Conclusion Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome. PMID:20426858

Using self-report and adverse event measures to track health's impact on productivity in known groups.

PubMed

Allen, Harris M; Bunn, William B

2003-09-01

The use of survey data to measure and monitor health and productivity differences between groups is an issue of increasing importance. This article examines the capacity of productivity self-reports (derived from surveys) and adverse event measures (derived from administrative sources) to differentiate groups with a priori known characteristics. A replication strategy is used to test the contributions that productivity self-reports make, alone as well as above and beyond measures of adverse events, to the discrimination of 5 pairs of groups classified by clinical, job type, and demographic criteria. These tests are conducted on representative samples of the active, largely blue-collar employee population at International Truck and Engine Corporation. The results show that both productivity self-reports and adverse event measures differentiate and track known groups. Even in the presence of highly significant effects from adverse event measures, self-reports improve the assessment of productivity. We conclude that: 1) although the joint use of self-reports and adverse event measures is the better approach, practitioners can use self-reports with the expectation that this method will track group differences in health and productivity when adverse event measures are not available; and 2) survey self-reports make unique and independent contributions when adverse events measures are used.

Life adversity is associated with smoking relapse after a quit attempt.

PubMed

Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

2016-09-01

Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prognostic value of androgen receptor in triple negative breast cancer: A meta-analysis.

PubMed

Wang, Changjun; Pan, Bo; Zhu, Hanjiang; Zhou, Yidong; Mao, Feng; Lin, Yan; Xu, Qianqian; Sun, Qiang

2016-07-19

Androgen receptor (AR) is a promising therapeutic target for breast cancer. However, its prognostic value remains controversial in triple negative breast cancer (TNBC). Here we present a meta-analysis to investigate the correlation between AR expression and TNBC prognosis. Thirteen relevant studies with 2826 TNBC patients were included. AR positive rate was 24.4%. AR+ patients tended to have lower tumor grade (p< 0.001), but more lymph node metastases (p < 0.01). AR positivity was associated with prolonged disease free survival (HR 0.809, 95% CI = 0.659-0.995, p < 0.05), but had no significant impact on overall survival (HR 1.270, 95% CI=0.904-1.782, p = 0.168). No difference in survival existed between subgroups using different AR or estrogen receptor cutoff values. Literature search was performed in Pubmed, Embase and Cochrane Central Register of Controlled Trials databases to identify relevant articles on AR and TNBC prognosis. Fixed- and random-effect meta-analyses were conducted based on the heterogeneity of included studies. Heterogeneity and impacts of covariates were further evaluated by subgroup analyses and meta-regression. AR positivity is associated with lower risk of disease recurrence in TNBC. Further clinical studies are warranted to clarify its prognostic role on TNBC recurrence and survival.

Distress Due to Prognostic Uncertainty in Palliative Care: Frequency, Distribution, and Outcomes among Hospitalized Patients with Advanced Cancer.

PubMed

Gramling, Robert; Stanek, Susan; Han, Paul K J; Duberstein, Paul; Quill, Tim E; Temel, Jennifer S; Alexander, Stewart C; Anderson, Wendy G; Ladwig, Susan; Norton, Sally A

2018-03-01

Prognostic uncertainty is common in advanced cancer and frequently addressed during palliative care consultation, yet we know little about its impact on quality of life (QOL). We describe the prevalence and distribution of distress due to prognostic uncertainty among hospitalized patients with advanced cancer before palliative care consultation. We evaluate the association between this type of distress and overall QOL before and after palliative care consultation. Observational cohort study. Hospitalized patients with advanced cancer who receive a palliative care consultation at two geographically distant academic medical centers. At the time of enrollment, before palliative care consultation, we asked participants: "Over the past two days, how much have you been bothered by uncertainty about what to expect from the course of your illness?" (Not at all/Slightly/Moderately/Quite a Bit/Extremely). We defined responses of "Quite a bit" and "Extremely" to be indicative of substantial distress. Two hundred thirty-six participants completed the baseline assessment. Seventy-seven percent reported being at least moderately bothered by prognostic uncertainty and half reported substantial distress. Compared with others, those who were distressed by prognostic uncertainty (118/236) reported poorer overall QOL before palliative care consultation (mean QOL 3.8 out of 10 vs. 5.3 out of 10, p = < 0.001) and greater improvement in QOL following consultation (Adjusted difference in mean QOL change = 1.1; 95% confidence interval = 0.2, 2.0). Prognostic uncertainty is a prevalent source of distress among hospitalized patients with advanced cancer at the time of initial palliative care consultation. Distress from prognostic uncertainty is associated with lower levels of preconsultation QOL and with greater pre-post consultation improvement in the QOL.

Epilepsy and adverse quality of life in surgically resected meningioma.

PubMed

Tanti, M J; Marson, A G; Jenkinson, M D

2017-09-01

Meningiomas are common intracranial tumors, and despite surgery or therapy with anti-epileptic drugs (AEDs), many patients suffer from seizures. Epilepsy has a significant impact on quality of life (QoL) in non-tumor populations, but the impact of epilepsy on QoL in patients with meningioma is unknown. Our aim was to evaluate the impact of epilepsy on QoL in patients that have undergone resection of a benign meningioma. We recruited meningioma patients without epilepsy (n=109), meningioma patients with epilepsy (n=56), and epilepsy patients without meningioma (n=64). QoL was measured with the Short Form 36 version 2 (SF-36), the Functional Assessment of Cancer Therapy (FACT-BR), and the Liverpool Adverse Events Profile (LAEP). Regression analyses identified significant determinants of QoL. Patients with meningioma and epilepsy had poorer QoL scores than meningioma patients without epilepsy in all measures. In FACT-BR, this difference was significant. Multiple regression analyses demonstrated that current AED use had a greater impact on QoL scores than recent seizures. Other variables associated with impaired QoL included depression, unemployment, and meningioma attributed symptoms. Epilepsy has a negative impact on quality of life in patients with benign meningioma. AED use is correlated with impaired QoL and raised LAEP scores, suggesting that AEDs and adverse effects may have led to impaired QoL in our meningioma patients with epilepsy. The severity of epilepsy in our meningioma population was comparatively mild; therefore, a more conservative approach to AED therapy may be indicated in an attempt to minimize adverse effects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Systematic review of renal carcinoma prognostic factors.

PubMed

Lorente, D; Trilla, E; Meseguer, A; Planas, J; Placer, J; Celma, A; Salvador, C; Regis, L; Morote, J

2017-05-01

The natural history of renal cell carcinoma is heterogeneous. Some scenarios can be found in terms of clinical presentation, clinical evolution or type of recurrence (local/metastatic). The aim of this publication is to analyze the most important prognostic factors published in the literature. A literature review ob published papers was performed using the Pubmed, from first Motzer's classification published in 1999 to 2015, according to PRISMA declaration. Search was done using the following keywords: kidney neoplasm, kidney cancer, renal cell carcinoma, prognostic factors, mortality, survival and disease progression. Papers were classified according to level of evidence, the number of patients included and the type of study performed. The evolution in the knowledge of molecular pathways related to renal oncogenesis and the new targeted therapies has left to remain obsolete the old prognostic models. It's necessary to perform a continuous review to actualize nomograms and to adapt them to the new scenarios. Is necessary to perform a proper external validation of existing prognostic factors using prospective and multicentric studies to add them into the daily urologist clinical practice. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Adverse psychological outcomes following colposcopy and related procedures: a systematic review.

PubMed

O'Connor, M; Gallagher, P; Waller, J; Martin, C M; O'Leary, J J; Sharp, L

2016-01-01

Although colposcopy is the leading follow-up option for women with abnormal cervical cytology, little is known about its psychological consequences. We performed a systematic review to examine: (1) what, if any, are the adverse psychological outcomes following colposcopy and related procedures; (2) what are the predictors of adverse psychological outcomes post-colposcopy; and (3) what happens to these outcomes over time. Five electronic databases (PubMed, PsychINFO, CINAHL, Web of Science, Scopus) were searched for studies published in English between January 1986 and February 2014. Eligible studies assessed psychological wellbeing at one or more time-points post-colposcopy. Two reviewers independently screened titles and abstracts. Full texts of potentially eligible papers were reviewed. Data were abstracted from, and a quality appraisal performed of, eligible papers. Twenty-three papers reporting 16 studies were eligible. Colposcopy and related procedures can lead to adverse psychological outcomes, particularly anxiety. Ten studies investigated predictors of adverse psychological outcomes; management type and treatment had no impact on this. Seven studies investigated temporal trends in psychological outcomes post-colposcopy; findings were mixed, especially in relation to anxiety and distress. Studies were methodologically heterogeneous. Follow-up investigations and procedures for abnormal cervical cytology can cause adverse psychological outcomes among women. However, little is known about the predictors of these outcomes or how long they persist. There is a need for a more standardised approach to the examination of the psychological impact of colposcopy, especially longer-term outcomes. Follow-up investigations for abnormal cervical cytology can cause adverse psychological outcome among women. © 2015 Royal College of Obstetricians and Gynaecologists.

Impact of patient communication problems on the risk of preventable adverse events in acute care settings

PubMed Central

Bartlett, Gillian; Blais, Régis; Tamblyn, Robyn; Clermont, Richard J.; MacGibbon, Brenda

2008-01-01

Background Up to 50% of adverse events that occur in hospitals are preventable. Language barriers and disabilities that affect communication have been shown to decrease quality of care. We sought to assess whether communication problems are associated with an increased risk of preventable adverse events. Methods We randomly selected 20 general hospitals in the province of Quebec with at least 1500 annual admissions. Of the 145 672 admissions to the selected hospitals in 2000/01, we randomly selected and reviewed 2355 charts of patients aged 18 years or older. Reviewers abstracted patient characteristics, including communication problems, and details of hospital admission, and assessed the cause and preventability of identified adverse events. The primary outcome was adverse events. Results Of 217 adverse events, 63 (29%) were judged to be preventable, for an overall population rate of 2.7% (95% confidence interval [CI] 2.1%–3.4%). We found that patients with preventable adverse events were significantly more likely than those without such events to have a communication problem (odds ratio [OR] 3.00; 95% CI 1.43–6.27) or a psychiatric disorder (OR 2.35; 95% CI 1.09–5.05). Patients who were admitted urgently were significantly more likely than patients whose admissions were elective to experience an event (OR 1.64, 95% CI 1.07–2.52). Preventable adverse events were mainly due to drug errors (40%) or poor clinical management (32%). We found that patients with communication problems were more likely than patients without these problems to experience multiple preventable adverse events (46% v. 20%; p = 0.05). Interpretation Patients with communication problems appeared to be at highest risk for preventable adverse events. Interventions to reduce the risk for these patients need to be developed and evaluated. PMID:18519903

The evolving field of prognostication and risk stratification in MDS: Recent developments and future directions.

PubMed

Lee, Eun-Ju; Podoltsev, Nikolai; Gore, Steven D; Zeidan, Amer M

2016-01-01

The clinical course of patients with myelodysplastic syndromes (MDS) is characterized by wide variability reflecting the underlying genetic and biological heterogeneity of the disease. Accurate prediction of outcomes for individual patients is an integral part of the evidence-based risk/benefit calculations that are necessary for tailoring the aggressiveness of therapeutic interventions. While several prognostication tools have been developed and validated for risk stratification, each of these systems has limitations. The recent progress in genomic sequencing techniques has led to discoveries of recurrent molecular mutations in MDS patients with independent impact on relevant clinical outcomes. Reliable assays of these mutations have already entered the clinic and efforts are currently ongoing to formally incorporate mutational analysis into the existing clinicopathologic risk stratification tools. Additionally, mutational analysis holds promise for going beyond prognostication to therapeutic selection and individualized treatment-specific prediction of outcomes; abilities that would revolutionize MDS patient care. Despite these exciting developments, the best way of incorporating molecular testing for use in prognostication and prediction of outcomes in clinical practice remains undefined and further research is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Testbed for Data Fusion for Helicopter Diagnostics and Prognostics

DTIC Science & Technology

2003-03-01

and algorithm design and tuning in order to develop advanced diagnostic and prognostic techniques for air craft health monitoring . Here a...and development of models for diagnostics, prognostics , and anomaly detection . Figure 5 VMEP Server Browser Interface 7 Download... detections , and prognostic prediction time horizons. The VMEP system and in particular the web component are ideal for performing data collection

Complex karyotype in mantle cell lymphoma is a strong prognostic factor for the time to treatment and overall survival, independent of the MCL international prognostic index.

PubMed

Sarkozy, Clémentine; Terré, Christine; Jardin, Fabrice; Radford, Isabelle; Roche-Lestienne, Catherine; Penther, Dominique; Bastard, Christian; Rigaudeau, Sophie; Pilorge, Sylvain; Morschhauser, Franck; Bouscary, Didier; Delarue, Richard; Farhat, Hassan; Rousselot, Philippe; Hermine, Olivier; Tilly, Hervé; Chevret, Sylvie; Castaigne, Sylvie

2014-01-01

Mantle cell lymphoma (MCL) is usually an aggressive disease. However, a few patients do have an "indolent" evolution (iMCL) defined by a long survival time without intensive therapy. Many studies highlight the prognostic role of additional genetic abnormalities, but these abnormalities are not routinely tested for and do not yet influence the treatment decision. We aimed to evaluate the prognostic impact of these additional abnormalities detected by conventional cytogenetic testing, as well as their relationships with the clinical characteristics and their value in identifying iMCL. All consecutive MCL cases diagnosed between 1995 and 2011 at four institutions were retrospectively selected on the basis of an informative karyotype with a t(11;14) translocation at the time of diagnosis. A total of 125 patients were included and followed for an actual median time of 35 months. The median overall survival (OS) and survival without treatment (TFS) were 73.7 and 1.3 months, respectively. In multivariable Cox models, a high mantle cell lymphoma international prognostic index score, a complex karyotype, and blastoid morphology were independently associated with a shortened OS. Spleen enlargement, nodal presentation, extra-hematological involvement, and complex karyotypes were associated with shorter TFS. A score based on these factors allowed for the identification of "indolent" patients (median TFS 107 months) from other patients (median TFS: 1 month). In conclusion, in this multicentric cohort of MCL patients, a complex karyotype was associated with a shorter survival time and allowed for the identification of iMCL at the time of diagnosis. Copyright © 2013 Wiley Periodicals, Inc.

Prognostic impact of subclinical or manifest extracoronary artery diseases after acute myocardial infarction.

PubMed

Eriksson Östman, Maja; Calais, Fredrik; Rosenblad, Andreas; Fröbert, Ole; Leppert, Jerzy; Hedberg, Pär

2017-08-01

In patients with coronary artery disease (CAD), clinically overt extracoronary artery diseases (ECADs), including claudication or previous strokes, are associated with poor outcomes. Subclinical ECADs detected by screening are common among such patients. We aimed to evaluate the prognostic impact of subclinical versus symptomatic ECADs in patients with acute myocardial infarction (AMI). In a prospective observational study, 654 consecutive patients diagnosed with AMI underwent ankle brachial index (ABI) measurements and ultrasonographic screening of the carotid arteries and abdominal aorta. Clinical ECADs were defined as prior strokes, claudication, or extracoronary artery intervention. Subclinical ECADs were defined as the absence of a clinical ECAD in combination with an ABI ≤0.9 or >1.4, carotid artery stenosis, or an abdominal aortic aneurysm. At baseline, subclinical and clinical ECADs were prevalent in 21.6% and 14.4% of the patients, respectively. Patients with ECADs received evidence-based medication more often at admission but similar medications at discharge compared with patients without ECADs. During a median follow-up of 5.2 years, 166 patients experienced endpoints of hospitalization for AMI, heart failure, stroke, or cardiovascular death. With ECAD-free cases as reference and after adjustment for risk factors, a clinical ECAD (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.34-3.27, p=0.001), but not a subclinical ECAD (HR 1.35, 95% CI 0.89-2.05, p=0.164), was significantly associated with worse outcomes. Despite receiving similar evidence-based medication at discharge, patients with clinical ECAD, but not patients with a subclinical ECAD, had worse long-term prognosis than patients without an ECAD after AMI. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A new prognostic score for AIDS-related lymphomas in the rituximab-era

PubMed Central

Barta, Stefan K.; Xue, Xiaonan; Wang, Dan; Lee, Jeannette Y.; Kaplan, Lawrence D.; Ribera, Josep-Maria; Oriol, Albert; Spina, Michele; Tirelli, Umberto; Boue, Francois; Wilson, Wyndham H.; Wyen, Christoph; Dunleavy, Kieron; Noy, Ariela; Sparano, Joseph A.

2014-01-01

While the International Prognostic Index is commonly used to predict outcomes in immunocompetent patients with aggressive B-cell non-Hodgkin lymphomas, HIV-infection is an important competing risk for death in patients with AIDS-related lymphomas. We investigated whether a newly created prognostic score (AIDS-related lymphoma International Prognostic Index) could better assess risk of death in patients with AIDS-related lymphomas. We randomly divided a dataset of 487 patients newly diagnosed with AIDS-related lymphomas and treated with rituximab-containing chemoimmunotherapy into a training (n=244) and validation (n=243) set. We examined the association of HIV-related and other known risk factors with overall survival in both sets independently. We defined a new score (AIDS-related lymphoma International Prognostic Index) by assigning weights to each significant predictor [age-adjusted International Prognostic Index, extranodal sites, HIV-score (composed of CD4 count, viral load, and prior history of AIDS)] with three risk categories similar to the age-adjusted International Prognostic Index (low, intermediate and high risk). We compared the prognostic value for overall survival between AIDS-related lymphoma International Prognostic Index and age-adjusted International Prognostic Index in the validation set and found that the AIDS-related lymphoma International Prognostic Index performed significantly better in predicting risk of death than the age-adjusted International Prognostic Index (P=0.004) and better discriminated risk of death between each risk category (P=0.015 vs. P=0.13). Twenty-eight percent of patients were defined as low risk by the ARL-IPI and had an estimated 5-year overall survival (OS) of 78% (52% intermediate risk, 5-year OS 60%; 20% high risk, 5-year OS 50%). PMID:25150257

Lifecycle Prognostics Architecture for Selected High-Cost Active Components

DOE Office of Scientific and Technical Information (OSTI.GOV)

N. Lybeck; B. Pham; M. Tawfik

There are an extensive body of knowledge and some commercial products available for calculating prognostics, remaining useful life, and damage index parameters. The application of these technologies within the nuclear power community is still in its infancy. Online monitoring and condition-based maintenance is seeing increasing acceptance and deployment, and these activities provide the technological bases for expanding to add predictive/prognostics capabilities. In looking to deploy prognostics there are three key aspects of systems that are presented and discussed: (1) component/system/structure selection, (2) prognostic algorithms, and (3) prognostics architectures. Criteria are presented for component selection: feasibility, failure probability, consequences of failure,more » and benefits of the prognostics and health management (PHM) system. The basis and methods commonly used for prognostics algorithms are reviewed and summarized. Criteria for evaluating PHM architectures are presented: open, modular architecture; platform independence; graphical user interface for system development and/or results viewing; web enabled tools; scalability; and standards compatibility. Thirteen software products were identified and discussed in the context of being potentially useful for deployment in a PHM program applied to systems in a nuclear power plant (NPP). These products were evaluated by using information available from company websites, product brochures, fact sheets, scholarly publications, and direct communication with vendors. The thirteen products were classified into four groups of software: (1) research tools, (2) PHM system development tools, (3) deployable architectures, and (4) peripheral tools. Eight software tools fell into the deployable architectures category. Of those eight, only two employ all six modules of a full PHM system. Five systems did not offer prognostic estimates, and one system employed the full health monitoring suite but lacked

Adverse Selection and Inertia in Health Insurance Markets: When Nudging Hurts.

PubMed

Handel, Benjamin R

2013-12-01

This paper investigates consumer inertia in health insurance markets, where adverse selection is a potential concern. We leverage a major change to insurance provision that occurred at a large firm to identify substantial inertia, and develop and estimate a choice model that also quantifies risk preferences and ex ante health risk. We use these estimates to study the impact of policies that nudge consumers toward better decisions by reducing inertia. When aggregated, these improved individual-level choices substantially exacerbate adverse selection in our setting, leading to an overall reduction in welfare that doubles the existing welfare loss from adverse selection.

Inflammation-based prognostic score and number of lymph node metastases are independent prognostic factors in esophageal squamous cell carcinoma.

PubMed

Kobayashi, Takashi; Teruya, Masanori; Kishiki, Tomokazu; Kaneko, Susumu; Endo, Daisuke; Takenaka, Yoshiharu; Miki, Kenji; Kobayashi, Kaoru; Morita, Koji

2010-08-01

Few studies have investigated whether the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score, is useful for postoperative prognosis of esophageal squamous cell carcinoma. GPS was calculated on the basis of admission data as follows: patients with elevated C-reactive protein level (>10 mg/l) and hypoalbuminemia (<35 g/l) were assigned to GPS2. Patients with one or no abnormal value were assigned to GPS1 or GPS0. A new scoring system was constructed using independent prognostic variables and was evaluated on whether it could be used to dictate the choice of clinical options. 65 patients with esophageal squamous cell carcinoma were enrolled. GPS and the number of lymph node metastases were found to be independent prognostic variables. The scoring system comprising GPS and the number of lymph node metastases was found to be effective in the prediction of a long-term outcome (p < 0.0001). Preoperative GPS may be useful for postoperative prognosis of patients with esophageal squamous cell carcinoma. GPS and the number of lymph node metastases could be used to identify a subgroup of patients with esophageal squamous cell carcinoma who are eligible for radical resection but show poor prognosis.

A systematic review of prognostic factors for return to work following work-related traumatic hand injury.

PubMed

Shi, Qiyun; Sinden, Kathryn; MacDermid, Joy C; Walton, David; Grewal, Ruby

2014-01-01

Systematic review. Traumatic hand injuries are frequent cause of work related injuries and can result in prolonged durations of time loss from work. To systematically review available evidence to determine which prognostic factors predict return-to-work (RTW) following work-related traumatic hand injuries. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO from 1980 to September 2013 and reference lists of articles. Studies investigating any prognostic factors of RTW after traumatic hand injury were included. Two reviewers performed study selection, assessment of methodological quality and data extraction independently of each other. Identified factors were grouped into conceptual prognostic factor categories. We assessed 8 studies, which addressed 11 potential prognostic factors (i.e., sociodemographic factors, occupation, work compensation status, treatment related factors, impairment severity, location of injury, etc.). The quality of the studies was low to moderate. Across all included studies, RTW (original or modified work) occurred in over 60% of individuals by 6 months. There was consistent low-moderate quality evidence that individuals with more severe impairments and lower pre-injury income were less likely to RTW, and low-moderate quality evidence that age, gender and level of education had no impact on RTW. Evidence on other commonly cited prognostic factors were limited in the literature. Impairment severity and lower pre-injury income showed a consistent association with RTW following occupational hand injury, while other factors demonstrated no or variable effects across studies. Additional high-quality studies are warranted toward improving our understanding of the complex factors that mediate RTW following a traumatic work-related hand injury. 2a. Copyright © 2014 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

NEDD9, an independent good prognostic factor in intermediate-risk acute myeloid leukemia patients

PubMed Central

Pallarès, Victor; Hoyos, Montserrat; Chillón, M. Carmen; Barragán, Eva; Conde, M. Isabel Prieto; Llop, Marta; Céspedes, María Virtudes; Nomdedeu, Josep F.; Brunet, Salut; Sanz, Miguel Ángel; González-Díaz, Marcos; Sierra, Jorge; Casanova, Isolda; Mangues, Ramon

2017-01-01

Intermediate-risk acute myeloid leukemia (IR-AML) is the largest subgroup of AML patients and is highly heterogeneous. Whereas adverse and favourable risk patients have well-established treatment protocols, IR-AML patients have not. It is, therefore, crucial to find novel factors that stratify this subgroup to implement risk-adapted strategies. The CAS (Crk-associated substrate) adaptor protein family regulates cell proliferation, survival, migration and adhesion. Despite its association with metastatic dissemination and prognosis of different solid tumors, the role of these proteins in hematological malignancies has been scarcely evaluated. Nevertheless, previous work has established an important role for the CAS family members NEDD9 or BCAR1 in the migratory and dissemination capacities of myeloid cells. On this basis, we hypothesized that NEDD9 or BCAR1 expression levels could associate with survival in IR-AML patients and become new prognostic markers. To that purpose, we assessed BCAR1 and NEDD9 gene expression in a cohort of 73 adult AML patients validating the results in an independent cohort (n = 206). We have identified NEDD9, but not BCAR1, as a new a marker for longer overall and disease-free survival, and for lower cumulative incidence of relapse. In summary, NEDD9 gene expression is an independent prognostic factor for favourable prognosis in IR-AML patients. PMID:29100287

Low CLL-1 Expression Is a Novel Adverse Predictor in 123 Patients with De Novo CD34+ Acute Myeloid Leukemia.

PubMed

Wang, Yan-Yu; Chen, Wen-Lian; Weng, Xiang-Qin; Sheng, Yan; Wu, Jing; Hao, Jie; Liu, Zhan-Yun; Zhu, Yong-Mei; Chen, Bing; Xiong, Shu-Min; Chen, Yu; Chen, Qiu-Sheng; Sun, Hui-Ping; Li, Jun-Min; Wang, Jin

2017-10-15

Recent reports state that C-type lectin-like molecule-1 (CLL-1) in acute myeloid leukemia (AML) is expressed primarily on myeloid cells, but there is still no investigation about its prognostic significance on leukemic blast compartment. Hence, this study aimed to evaluate the prognostic value of CLL-1 in 123 patients with de novo CD34 + Non-M3 AML. Multiparameter flow cytometry was used to assess the expression of CLL-1 on immature compartment in AML and control groups. We found that CLL-1 expression level on blast compartment was closely linked to clinical characteristics, treatment response, and survival outcome of patients. Decreased expression of CLL-1 was observed on immature compartment from AML patients as compared with controls (62.6% vs. 86.5%, P < 0.05). Logistic model exhibited that CLL-1 low independently predicted low complete remission rate with an odds ratio of 4.57 (2.53-6.61, P < 0.05). Additionally, CLL-1 expression level at diagnosis was inversely correlated to the residual blast cells (residual leukemia cell) after induction chemotherapy (r = -0.423, P < 0.05). Furthermore, multivariate Cox regression model demonstrated that CLL-1 low was still an independent adverse predictor (P < 0.05 for event-free survival, P < 0.05 for overall survival). Notably, CLL-1 low was able to discriminate poor survival patients from intermediate- and favorable-risk groups. Taken together, CLL-1 is a novel prognostic predictor that could be exploited to supplement the current AML prognostic risk stratification system, and potentially optimize the clinical management of AML.

Prognostic Value of Negative Coronary CT Angiography in Severely Obese Patients Prior to Bariatric Surgery: a Follow-Up After 6 Years.

PubMed

Messerli, Michael; Maywald, Céline; Wälti, Stephan; Warschkow, René; Wildermuth, Simon; Alkadhi, Hatem; Leschka, Sebastian; Schiesser, Marc

2017-08-01

This study aims to determine the long-term prognostic value of coronary CT angiography (CCTA) prior to bariatric surgery in severely obese patients with a body mass index (BMI) ≥35 kg/m 2 . Seventy consecutive patients undergoing cardiac CT for coronary assessment prior to bariatric surgery were prospectively included. Images were analysed for the presence of coronary calcification and for non-obstructive (<50%) or obstructive (>50% stenosis) coronary artery disease (CAD). A median clinical follow-up of 6.1 years in 54 patients was obtained for major adverse cardiovascular events (MACEs), defined as death, non-fatal myocardial infarction or coronary revascularisation. Weight loss and BMI decrease following bariatric surgery were recorded. The median BMI prior to surgery was 46.9 kg/m 2 . The median percentage of excess BMI loss after surgery was 75%. CT showed coronary calcification in 26 (48%) patients, whereas 28 (52%) patients had no calcification. CCTA revealed normal coronaries in 47 (87%) and non-obstructive CAD in 7 (13%) patients. No obstructive CAD was found. All patients successfully underwent bariatric surgery, and no MACE occurred neither perioperatively nor in the follow-up period. The negative predictive value of CCTA was 100% (95% confidence interval of 90.1-100.0%). In severely obese patients, the absence of obstructive CAD in cardiac CT prior to bariatric surgery with subsequently marked weight reduction has strong long-term prognostic implications for ruling out major adverse cardiac events in the postoperative period.

Prognostic value of cardiovascular magnetic resonance imaging measurements corrected for age and sex in idiopathic pulmonary arterial hypertension.

PubMed

Swift, Andrew J; Rajaram, Smitha; Campbell, Michael J; Hurdman, Judith; Thomas, Steve; Capener, Dave; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

2014-01-01

There are limited data on the prognostic value of cardiovascular magnetic resonance measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of cardiovascular magnetic resonance indices for age and sex on prognostic value. Consecutive patients with idiopathic pulmonary arterial hypertension underwent cardiovascular magnetic resonance imaging at 1.5T. Steady-state free precession cardiac volumes and mass measurements were corrected for age, sex, and body surface area according to reference data and prognostic significance assessed. A total of 80 patients with idiopathic pulmonary arterial hypertension were identified, and 23 patients died during the mean follow-up of 32±14 months. Corrected for age, sex, and body surface area, right ventricular end-systolic volume (P=0.004) strongly predicted mortality, independent of World Health Organization functional class, mean right atrial pressure, cardiac index, and mixed venous oxygen saturations. Consideration should be given to correcting cardiovascular magnetic resonance measures for age, sex, and body surface area, particularly given the changing demographics of patients with idiopathic pulmonary arterial hypertension. Corrected right ventricular end-systolic volume is a strong prognostic marker in idiopathic pulmonary arterial hypertension, independent of invasively derived measurements, mean right atrial pressure cardiac index, and mixed venous oxygen saturations.

Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer

PubMed Central

Sperduti, Isabella; Iapicca, Pierluigi; Visca, Paolo; Alessandrini, Gabriele; Antoniani, Barbara; Pilotto, Sara; Ludovini, Vienna; Vannucci, Jacopo; Bellezza, Guido; Sidoni, Angelo; Tortora, Giampaolo; Radisky, Derek C.; Crinò, Lucio; Cognetti, Francesco; Facciolo, Francesco; Mottolese, Marcella

2014-01-01

Risk assessment and treatment choice remain a challenge in early non-small-cell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and hMENAΔv6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENAΔv6. Enforced expression of hMENAΔv6 or hMENA11a increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA11a were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA11a was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low pan-hMENA/high hMENA11a expression fared significantly better (P≤0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk. PMID:25373410

Systematic review of current prognostication systems for primary gastrointestinal stromal tumors.

PubMed

Khoo, Chun Yuet; Chai, Xun; Quek, Richard; Teo, Melissa C C; Goh, Brian K P

2018-04-01

The advent of tyrosine kinase inhibitors as adjuvant therapy has revolutionized the management of GIST and emphasized the need for accurate prognostication systems. Numerous prognostication systems have been proposed for GIST but at present it remains unknown which system is superior. The present systematic review aims to summarize current prognostication systems for primary treatment-naive GIST. A literature review of the Pubmed and Embase databases was performed to identify all published articles in English, from the 1st January 2002 to 28th Feb 2017, reporting on clinical prognostication systems of GIST. Twenty-three articles on GIST prognostication systems were included. These systems were classified as categorical systems, which stratify patients into risk groups, or continuous systems, which provide an individualized form of risk assessment. There were 16 categorical systems in total. There were 4 modifications of the National Institute of Health (NIH) system, 2 modifications of Armed Forces Institute of Pathology (AFIP) criteria and 3 modifications of Joensuu (modified NIH) criteria. Of the 7 continuous systems, there were 3 prognostic nomograms, 3 mathematical models and 1 prognostic heat/contour maps. Tumor size, location and mitotic count remain the main variables used in these systems. Numerous prognostication systems have been proposed for the risk stratification of GISTs. The most widely used systems today are the NIH, Joensuu modified NIH, AFIP and the Memorial Sloan Kettering Cancer Center nomogram. More validation and comparison studies are required to determine the optimal prognostication system for GIST. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

A Distributed Approach to System-Level Prognostics

DTIC Science & Technology

2012-09-01

the end of (useful) life ( EOL ) and/or the remaining useful life (RUL) of components, subsystems, or systems. The prognostics problem itself can be...system state estimate, computes EOL and/or RUL. In this paper, we focus on a model-based prognostics approach (Orchard & Vachtse- vanos, 2009; Daigle...been focused on individual components, and determining their EOL and RUL, e.g., (Orchard & Vachtsevanos, 2009; Saha & Goebel, 2009; Daigle & Goebel

Community-Acquired Meningitis in Older Adults: Clinical Features, Etiology, and Prognostic Factors

PubMed Central

Wang, Amy Y.; Machicado, Jorge D.; Khoury, Nabil T.; Wootton, Susan H.; Salazar, Lucrecia; Hasbun, Rodrigo

2014-01-01

Background Bacterial meningitis in older adults is a well-studied and serious disease, but few studies have investigated the epidemiology and outcomes of community-acquired meningitis in older adults. Methods We conducted a retrospective study of 619 adults in Houston, Texas, with community-acquired meningitis hospitalized between January 1, 2005, and January 1, 2010. Patients were categorized as older if age ≥65 (N=54) and younger if age 18–64 (N=565). An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less. Results Older patients consisted of 8.7% (54/619) of the total cohort and had higher rates of comorbidities, abnormal neurological and laboratory findings, abnormalities on computed tomography and magnetic resonance imaging of the head and adverse clinical outcomes (ACO) (p<0.05). The majority of patients (65.8%) had meningitis of unknown etiology. Bacterial meningitis was an infrequent cause (7.4%). Of the known causes, bacterial meningitis and West Nile virus were more common in older patients. In contrast, younger patients more frequently had cryptococcal and viral meningitis. On logistic regression, female gender was predictive of a poor outcome in the older patients, whereas abnormal neurologic exam, fever, and CSF glucose <45mg/dLwere significant poor prognostic factors in younger patients (p<0.05). Conclusion Most cases of community-acquired meningitis are of unknown origin. Older patients are more likely to have bacterial meningitis and West Nile virus infection when a cause can be identified. They also have more neurologic abnormalities, laboratory and imaging abnormalities, as well as adverse clinical outcomes. PMID:25370434

The Prognostic Value of the Left Ventricular Ejection Fraction Is Dependent upon the Severity of Mitral Regurgitation in Patients with Acute Myocardial Infarction

PubMed Central

Cho, Jung Sun; Youn, Ho-Joong; Her, Sung-Ho; Park, Maen Won; Kim, Chan Joon; Park, Gyung-Min; Cho, Jae Yeong; Ahn, Youngkeun; Kim, Kye Hun; Park, Jong Chun; Seung, Ki Bae; Cho, Myeong Chan; Kim, Chong Jin; Kim, Young Jo; Han, Kyoo Rok; Kim, Hyo Soo

2015-01-01

The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF ≤ 40% (n = 2,422 and 197, respectively) and LVEF > 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age ≥ 75 yr, Killip class ≥ III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high-sensitivity C-reactive protein ≥ 2.59 mg/L, LVEF ≤ 40%, estimated glomerular filtration rate (eGFR), and percutaneous coronary intervention (PCI). However, PCI was an independent predictor in AMI patients with high-grade MR. No differences in primary endpoints between AMI patients with high-grade MR (grades 3-4) and EF ≤ 40% or EF > 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR. PMID:26130953

All Unhappy Childhoods Are Unhappy in Their Own Way-Differential Impact of Dimensions of Adverse Childhood Experiences on Adult Mental Health and Health Behavior.

PubMed

Westermair, Anna L; Stoll, Anne M; Greggersen, Wiebke; Kahl, Kai G; Hüppe, Michael; Schweiger, Ulrich

2018-01-01

Adverse childhood experiences have consistently been linked with poor mental and somatic health in adulthood. However, due to methodological restraints of the main lines of research using cumulative or selective models, little is known about the differential impact of different dimensions of adverse childhood experiences. Therefore, we gathered data from 396 psychiatric in-patients on the Adverse Childhood Experiences (ACE) questionnaire, extracted dimensions using factor analysis and compared this dimensional model of adverse childhood experiences to cumulative and selective models. Household Dysfunction (violence against the mother, parental divorce, substance abuse or incarceration of a household member) was associated with poor health behaviors (smoking, alcohol dependency and obesity as proxy marker for an imbalance between energy intake and physical activity) and with poorer socio-economic achievement (lower education and income) in adulthood. The previously reported associations of maltreatment and sexual abuse with these outcome criteria could not be corroborated. Both Maltreatment (emotional and physical neglect and abuse) and Sexual Abuse predicted BPD, PTSD and suicidal behavior. However, the two ACE dimensions showed sufficiently divergent validity to warrant separate consideration in future studies: Maltreatment was associated with affective and anxiety disorders such as social phobia, panic disorder and major depressive disorder, whereas Sexual Abuse was associated with dysregulation of bodily sensations such as pain intensity and hunger/satiation. Also, we found both quantitative and qualitative evidence for the superiority of the dimensional approach to exploring the consequences of adverse childhood experiences in comparison to the cumulative and selective approaches.

Prognostic factors in Acanthamoeba keratitis.

PubMed

Kaiserman, Igor; Bahar, Irit; McAllum, Penny; Srinivasan, Sathish; Elbaz, Uri; Slomovic, Allan R; Rootman, David S

2012-06-01

To assess the prognostic factors influencing visual prognosis and length of treatment after acanthamoeba keratitis (AK). Forty-two AK eyes of 41 patients treated between 1999 and 2006 were included. A diagnosis of AK was made on the basis of culture results with a corresponding clinical presentation. We calculated the prognostic effect of the various factors on final visual acuity and the length of treatment. Multivariate regression analysis was used to adjust for the simultaneous effects of the various prognostic factors. Mean follow-up was 19.7 ± 21.0 months. Sixty-four percent of cases had > 1 identified risk factor for AK, the most common risk factor being contact lens wear (92.9% of eyes). At presentation, median best spectacle corrected visual acuity (BCVA) was 20/200 (20/30 to Hand Motion [HM]) that improved after treatment to 20/50 (20/20 to Counting Fingers [CF]). Infection acquired by swimming or related to contact lenses had significantly better final BCVA (p = 0.03 and p = 0.007, respectively). Neuritis and pseudodendrites were also associated with better final BCVA (p = 0.04 and p = 0.05, respectively). Having had an epithelial defect on presentation and having been treated with topical steroid were associated with worse final best spectacle corrected visual acuity (BSCVA) (p = 0.0006 and p = 0.04). Multivariate regression analysis found a good initial visual acuity (p = 0.002), infections related to swimming (p = 0.01), the absence of an epithelial defect (p = 0.03), having been treated with chlorhexidine (p = 0.05), and not having receive steroids (p = 0.003) to significantly forecast a good final BCVA. We identified several prognostic factors that can help clinicians evaluate the expected visual damage of the AK infection and thus tailor treatment accordingly. Copyright © 2012 Canadian Ophthalmological Society. All rights reserved.

The Relationship Between Human Papillomavirus Status and Other Molecular Prognostic Markers in Head and Neck Squamous Cell Carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, Christina S.; Narasimhan, Balasubramanian; Cao Hongbin

2009-06-01

Purpose: To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status. Methods and Materials: HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16{sup INK4a} staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO{sub 2} and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining). Results: Forty-four percent of evaluable tumorsmore » had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16{sup INK4a} staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16{sup INK4a} staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO{sub 2} or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(-) tumors. Conclusion: HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(-) tumors.« less

Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes.

PubMed

Solé, Francesc; Luño, Elisa; Sanzo, Carmen; Espinet, Blanca; Sanz, Guillermo F; Cervera, José; Calasanz, María José; Cigudosa, Juan Cruz; Millà, Fuensanta; Ribera, Josep Maria; Bureo, Encarna; Marquez, Maria Luisa; Arranz, Eva; Florensa, Lourdes

2005-09-01

The main prognostic factors in myelodysplastic syndromes (MDS) are chromosomal abnormalities, the proportion of blasts in bone marrow and number and degree of cytopenias. A consensus-defined International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in MDS has been developed, but its prognostic value in a large and independent series remains unproven. Furthermore, the intermediate-risk cytogenetic subgroup defined by the IPSS includes a miscellaneous number of different single abnormalities of uncertain prognostic significance at present. The main aim of the present study was to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in order to find new cytogenetic markers with predictive value. We report the cytogenetic findings in a series of 968 patients with primary MDS from the Spanish Cytogenetics Working Group, Grupo Cooperativo Español de Citogenética Hematológica (GCECGH). In this series of 968 MDS patients, we found various cytogenetic aberrations with a new prognostic impact. Complex karyotype, -7/7q- and i(17q) had a poor prognosis; normal karyotype, loss of Y chromosome, deletion 11q, deletion 12p and deletion 20q as single alterations had a good prognosis. Intermediate prognosis aberrations were rearrangements of 3q21q26, trisomy 8, trisomy 9, translocations of 11q and del(17p). Finally, a new group of single or double cytogenetic abnormalities, most of which are considered rare cytogenetic events and are usually included in the intermediate category of the IPSS, showed a trend to poor prognosis. This study suggests that some specific chromosomal abnormalities could be segregated from the IPSS intermediate-risk cytogenetic prognostic subgroup and included in the low risk or in the poor risk groups.

Close Friends' Psychopathology as a Pathway From Early Adversity to Young Adulthood Depressive Symptoms.

PubMed

Raposa, Elizabeth B; Hammen, Constance L; Brennan, Patricia A

2015-01-01

Past research has highlighted the negative impact of early adverse experiences on childhood social functioning, including friendship selection, and later mental health. The current study explored the long-term effects of early adversity on young adults' close friends' psychological symptoms and the impact of these close friendships on later depressive symptoms. A prospective longitudinal design was used to examine 816 youth from a large community-based sample, who were followed from birth through age 25. Participants' mothers provided contemporaneous information about adversity exposure up to age 5, and participants completed questionnaires about their own depressive symptoms at age 20 and in their early 20s. Youth also nominated a best friend to complete questionnaires about his or her own psychopathology at age 20. Individuals who experienced more early adversity by age 5 had best friends with higher rates of psychopathology at age 20. Moreover, best friends' psychopathology predicted target youth depressive symptoms 2 to 5 years later. Results indicate that early adversity continues to affect social functioning throughout young adulthood and that best friendships marked by elevated psychopathology in turn negatively affect mental health. Findings have implications for clinical interventions designed to prevent the development of depressive symptoms in youth who have been exposed to early adversity.

Close Friends’ Psychopathology as a Pathway from Early Adversity to Young Adulthood Depressive Symptoms

PubMed Central

Raposa, Elizabeth; Hammen, Constance; Brennan, Patricia

2014-01-01

Objective Past research has highlighted the negative impact of early adverse experiences on childhood social functioning, including friendship selection, and later mental health. The current study explored the long-term effects of early adversity on young adults’ close friends’ psychological symptoms, and the impact of these close friendships on later depressive symptoms. Method A prospective longitudinal design was used to examine 816 youth from a large community-based sample, who were followed from birth through age 25. Participants’ mothers provided contemporaneous information about adversity exposure prior to age 5, and participants completed questionnaires about their own depressive symptoms at age 20 and in their early 20’s. Youth also nominated a best friend to complete questionnaires about their own psychopathology at age 20. Results Individuals who experienced more early adversity by age 5 had best friends with higher rates of psychopathology at age 20. Moreover, best friends’ psychopathology predicted target youth depressive symptoms two to five years later. Conclusions Results indicate that early adversity continues to affect social functioning throughout young adulthood, and that best friendships marked by elevated psychopathology in turn negatively affect mental health. Findings have implications for clinical interventions designed to prevent the development of depressive symptoms in youth who have been exposed to early adversity. PMID:24871609

Prognostic markers in localized prostate cancer: from microscopes to molecules.

PubMed

Harding, M A; Theodorescu, D

Management of patients diagnosed with localized prostate cancer is complicated by the diverse natural history of the disease and variable response to treatment. Prognostic criteria currently in use cannot fully predict tumor behavior and thus limit the ability to recommend treatment regimens with the assurance that they are the best course of action for each individual patient. The search for better prognostic markers is now focussed on the molecular mechanisms which underlay tumor behavior, such as altered cell cycle progression, apoptosis, neuroendocrine differentiation, and angiogenesis. As the number of potential molecular markers increases, it is becoming evident that no single marker will provide the prognostic information necessary to make a significant improvement in patient care. In addition, it seems likely that traditional methods of assessing the prognostic value of this multitude of new markers will prove inadequate. In this review, we briefly examine the current state of prognostication in localized prostate cancer and some of the promising new molecular markers. Next, we examine how new technologies may allow the multiplex analysis of vast numbers of markers and how computational methods such as artificial neural networks will provide meaningful interpretation of the data. In the near future, such an integrated approach may provide a comprehensive prognostic tool for localized prostate cancer.

Vaccine Adverse Events

MedlinePlus

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The impact of herbal remedies on adverse effects and quality of life in HIV-infected individuals on antiretroviral therapy

PubMed Central

Bepe, Nyasha; Madanhi, Nathan; Mudzviti, Tinashe; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D

2012-01-01

Introduction Use of herbal remedies among HIV-infected individuals in Africa increased in the past decade, mainly due to traditional beliefs and at times inconsistent access to antiretroviral drugs. In Zimbabwe, accessibility and availability of antiretroviral drugs has increased in recent years; however, the use of herbal remedies remains high. This study was conducted to determine the impact of concomitant use of herbal remedies with antiretroviral drugs on adverse events and on quality of life. Methodology A convenient sample of HIV positive patients at Parirenyatwa group of hospitals' Family Care Clinic (Harare, Zimbabwe) was enrolled. A questionnaire was used to collect data on the adverse event experiences of the patients using herbal remedies for their HIV, as well as the types of herbal remedy used. Quality of life index was measured using an HIV/AIDS targeted quality of life (HAT-QOL) tool developed by the World Health Organization. Results Abdominal pain (odds ratio = 2.7, p-value = 0.01) and rash (odds ratio = 2.5, p-value = 0.02) had significant associations with using herbal remedies during antiretroviral therapy. Improved quality of life index was not significantly associated with herbal remedy use during antiretroviral therapy. Conclusions There is evidence to suggest that some traditional herbal remedies used in Zimbabwe may increase incidence of certain types of adverse events when used in combination with antiretroviral drugs. Use of herbal drugs in combination with antiretroviral therapy does not significantly improve quality of life index in comparison to antiretroviral drug use only. PMID:21330740

Treatment-Related Predictive and Prognostic Factors in Trimodality Approach in Stage IIIA/N2 Non-Small Cell Lung Cancer.

PubMed

Jeremić, Branislav; Casas, Francesc; Dubinsky, Pavol; Gomez-Caamano, Antonio; Čihorić, Nikola; Videtic, Gregory; Igrutinovic, Ivan

2018-01-01

While there are no established pretreatment predictive and prognostic factors in patients with stage IIIA/pN2 non-small cell lung cancer (NSCLC) indicating a benefit to surgery as a part of trimodality approach, little is known about treatment-related predictive and prognostic factors in this setting. A literature search was conducted to identify possible treatment-related predictive and prognostic factors for patients for whom trimodality approach was reported on. Overall survival was the primary endpoint of this study. Of 30 identified studies, there were two phase II studies, 5 "prospective" studies, and 23 retrospective studies. No study was found which specifically looked at treatment-related predictive factors of improved outcomes in trimodality treatment. Of potential treatment-related prognostic factors, the least frequently analyzed factors among 30 available studies were overall pathologic stage after preoperative treatment and UICC downstaging. Evaluation of treatment response before surgery and by pathologic tumor stage after induction therapy were analyzed in slightly more than 40% of studies and found not to influence survival. More frequently studied factors-resection status, degree of tumor regression, and pathologic nodal stage after induction therapy as well as the most frequently studied factor, the treatment (in almost 75% studies)-showed no discernible impact on survival, due to conflicting results. Currently, it is impossible to identify any treatment-related predictive or prognostic factors for selecting surgery in the treatment of patients with stage IIIA/pN2 NSCLC.

[Prognostic value of JAK2, MPL and CALR mutations in Chinese patients with primary myelofibrosis].

PubMed

Xu, Z F; Li, B; Liu, J Q; Li, Y; Ai, X F; Zhang, P H; Qin, T J; Zhang, Y; Wang, J Y; Xu, J Q; Zhang, H L; Fang, L W; Pan, L J; Hu, N B; Qu, S Q; Xiao, Z J

2016-07-01

.7, respectively). The impact of the CALR type- 2 mutations or no detectable driver mutation on survival was independent of current prognostic scoring systems. The DIPSS- Chinese molecular prognostic model based on the molecular features of Chinese patients was proposed and worked well for prognostic indication.

Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma.

PubMed

Ren, Tong; Wang, Shu; Sun, Jian; Qu, Ji-Min; Xiang, Yang; Shen, Keng; Lang, Jing He

2017-10-03

Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored. We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months. Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients. EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.

Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament.

PubMed

Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A; Münsterkötter, Anna L; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter; Lonsdorf, Tina B

2016-04-01

Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. © The Author (2015). Published by Oxford University Press.

Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament

PubMed Central

Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A.; Münsterkötter, Anna L.; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter

2016-01-01

Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. PMID:26568620

Metabolic syndrome and the risk of adverse cardiovascular events after an acute coronary syndrome.

PubMed

Cavallari, Ilaria; Cannon, Christopher P; Braunwald, Eugene; Goodrich, Erica L; Im, KyungAh; Lukas, Mary Ann; O'Donoghue, Michelle L

2018-05-01

Background The incremental prognostic value of assessing the metabolic syndrome has been disputed. Little is known regarding its prognostic value in patients after an acute coronary syndrome. Design and methods The presence of metabolic syndrome (2005 International Diabetes Federation) was assessed at baseline in SOLID-TIMI 52, a trial of patients within 30 days of acute coronary syndrome (median follow-up 2.5 years). The primary endpoint was major coronary events (coronary heart disease death, myocardial infarction or urgent coronary revascularization). Results At baseline, 61.6% ( n = 7537) of patients met the definition of metabolic syndrome, 34.7% (n = 4247) had diabetes and 29.3% had both ( n = 3584). The presence of metabolic syndrome was associated with increased risk of major coronary events (adjusted hazard ratio (adjHR) 1.29, p < 0.0001) and recurrent myocardial infarction (adjHR 1.30, p < 0.0001). Of the individual components of the definition, only diabetes (adjHR 1.48, p < 0.0001) or impaired fasting glucose (adjHR 1.21, p = 0.002) and hypertension (adjHR 1.46, p < 0.0001) were associated with the risk of major coronary events. In patients without diabetes, metabolic syndrome was numerically but not significantly associated with the risk of major coronary events (adjHR 1.13, p = 0.06). Conversely, diabetes was a strong independent predictor of major coronary events in the absence of metabolic syndrome (adjHR 1.57, p < 0.0001). The presence of both diabetes and metabolic syndrome identified patients at highest risk of adverse outcomes but the incremental value of metabolic syndrome was not significant relative to diabetes alone (adjHR 1.07, p = 0.54). Conclusions After acute coronary syndrome, diabetes is a strong and independent predictor of adverse outcomes. Assessment of the metabolic syndrome provides only marginal incremental value once the presence or absence of diabetes is established.

A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial.

PubMed

Boyd, K D; Ross, F M; Chiecchio, L; Dagrada, G P; Konn, Z J; Tapper, W J; Walker, B A; Wardell, C P; Gregory, W M; Szubert, A J; Bell, S E; Child, J A; Jackson, G H; Davies, F E; Morgan, G J

2012-02-01

The association of genetic lesions detected by fluorescence in situ hybridization (FISH) with survival was analyzed in 1069 patients with newly presenting myeloma treated in the Medical Research Council Myeloma IX trial, with the aim of identifying patients associated with the worst prognosis. A comprehensive FISH panel was performed, and the lesions associated with short progression-free survival and overall survival (OS) in multivariate analysis were +1q21, del(17p13) and an adverse immunoglobulin heavy chain gene (IGH) translocation group incorporating t(4;14), t(14;16) and t(14;20). These lesions frequently co-segregated, and there was an association between the accumulation of these adverse FISH lesions and a progressive impairment of survival. This observation was used to define a series of risk groups based on number of adverse lesions. Taking this approach, we defined a favorable risk group by the absence of adverse genetic lesions, an intermediate group with one adverse lesion and a high-risk group defined by the co-segregation of >1 adverse lesion. This genetic grouping was independent of the International Staging System (ISS) and so was integrated with the ISS to identify an ultra-high-risk group defined by ISS II or III and >1 adverse lesion. This group constituted 13.8% of patients and was associated with a median OS of 19.4 months.

Lymph node ratio as a prognostic factor in metastatic cutaneous head and neck squamous cell carcinoma.

PubMed

Vasan, Kartik; Low, Tsu-Hui Hubert; Gupta, Ruta; Ashford, Bruce; Asher, Rebecca; Gao, Kan; Ch'ng, Sydney; Palme, Carsten E; Clark, Jonathan R

2018-05-01

The prognostic impact of the size and number of nodal metastases in head and neck cutaneous squamous cell carcinoma (SCC) is well established. The purpose of this study was to validate the prognostic significance of the lymph node ratio in metastatic head and neck cutaneous SCC. A retrospective review of 326 patients with head and neck cutaneous SCC with parotid and/or cervical nodal metastases was performed. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The minimal-P approach was used to investigate the optimal lymph node ratio threshold. Our data included 77 recurrences and 101 deaths. A lymph node ratio of 6% was a significant predictor of shorter DFS (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.11-2.38; P = .01) and OS (HR 1.63; 95% CI 1.03-2.58; P = 0.04) on multivariable analysis. The lymph node ratio is an independent prognosticator of survival outcomes in patients presenting with metastatic head and neck cutaneous SCC. A lymph node ratio >6% is a significant threshold to categorize patients into low and high risk. © 2018 Wiley Periodicals, Inc.

Prognostic factors for ovarian epithelial cancer in the elderly: a case-control study.

PubMed

Sabatier, Renaud; Calderon, Benoît; Lambaudie, Eric; Chereau, Elisabeth; Provansal, Magali; Cappiello, Maria-Antonietta; Viens, Patrice; Rousseau, Frederique

2015-06-01

Ovarian cancer is the leading cause of mortality by gynecologic cancers in Western countries. Many publications have suggested that age may be an independent prognostic factor in ovarian carcinoma. There are only few data concerning the impact of treatments and geriatric features within the elderly population. We collected data of older (≥ 70 years old) patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. First we described usual clinical and pathological features for these patients, as well as their outcome. We compared these parameters with that of young (<70 years old) patients treated during the same period. We then observed geriatric features in our set: Eastern Cooperative Oncology Group performance status, number of medications, Charlson index, body mass index, hemoglobin, and glomerular filtration rate. We finally looked for prognostic factors specific of the elderly population. One hundred nine elderly patients were identified and compared with 488 younger cases. There was no difference concerning clinicopathologic data. Surgery was more frequently complete in young women (58% vs 41.7%), and older patients received less chemotherapy courses and less taxanes (38.4% vs 67.1%). Young patients had a longer overall survival (median, 65.2 vs 26.2 months, P = 8.5E-10, log-rank test). Multivariate analyses confirmed that age was an independent prognostic factor and that within the elderly set the International Federation of Gynecology and Obstetrics stage, surgery results, number of chemotherapy cycles administered and performance status had a significant prognostic value. No clear correlation could be observed between geriatric characteristics and treatments administration. Ovarian cancer prognosis is poorer for older women, but they are more frequently suboptimally treated. No correlation could be observed between geriatric factors and surgery or chemotherapy achievement. Treatment decision should be based on objective

Prognostic value of long noncoding RNA MALAT1 in digestive system malignancies.

PubMed

Zhai, Hui; Li, Xiao-Mei; Maimaiti, Ailifeire; Chen, Qing-Jie; Liao, Wu; Lai, Hong-Mei; Liu, Fen; Yang, Yi-Ning

2015-01-01

MALAT1, a newly discovered long noncoding RNA (lncRNA), has been reported to be highly expressed in many types of cancers. This meta-analysis summarizes its potential prognostic value in digestive system malignancies. A quantitative meta-analysis was performed through a systematic search in PubMed, Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI) for eligible papers on the prognostic impact of MALAT1 in digestive system malignancies from inception to Apr. 25, 2015. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to summarize the effect. Five studies were included in the study, with a total of 527 patients. A significant association was observed between MALAT1 abundance and poor overall survival (OS) of patients with digestive system malignancies, with pooled hazard ratio (HR) of 7.68 (95% confidence interval [CI]: 4.32-13.66, P<0.001). Meta sensitivity analysis suggested the reliability of our findings. No publication bias was observed. MALAT1 abundance may serve as a novel predictive factor for poor prognosis in patients with digestive system malignancies.

Embedded Diagnostic/Prognostic Reasoning and Information Continuity for Improved Avionics Maintenance

DTIC Science & Technology

2006-01-01

enabling technologies such as built-in-test, advanced health monitoring algorithms, reliability and component aging models, prognostics methods, and...deployment and acceptance. This framework and vision is consistent with the onboard PHM ( Prognostic and Health Management) as well as advanced... monitored . In addition to the prognostic forecasting capabilities provided by monitoring system power, multiple confounding errors by electronic

Application of molecular biology of differentiated thyroid cancer for clinical prognostication.

PubMed

Marotta, Vincenzo; Sciammarella, Concetta; Colao, Annamaria; Faggiano, Antongiulio

2016-11-01

Although cancer outcome results from the interplay between genetics and environment, researchers are making a great effort for applying molecular biology in the prognostication of differentiated thyroid cancer (DTC). Nevertheless, role of molecular characterisation in the prognostic setting of DTC is still nebulous. Among the most common and well-characterised genetic alterations related to DTC, including mutations of BRAF and RAS and RET rearrangements, BRAF V600E is the only mutation showing unequivocal association with clinical outcome. Unfortunately, its accuracy is strongly limited by low specificity. Recently, the introduction of next-generation sequencing techniques led to the identification of TERT promoter and TP53 mutations in DTC. These genetic abnormalities may identify a small subgroup of tumours with highly aggressive behaviour, thus improving specificity of molecular prognostication. Although knowledge of prognostic significance of TP53 mutations is still anecdotal, mutations of the TERT promoter have showed clear association with clinical outcome. Nevertheless, this genetic marker needs to be analysed according to a multigenetic model, as its prognostic effect becomes negligible when present in isolation. Given that any genetic alteration has demonstrated, taken alone, enough specificity, the co-occurrence of driving mutations is emerging as an independent genetic signature of aggressiveness, with possible future application in clinical practice. DTC prognostication may be empowered in the near future by non-tissue molecular prognosticators, including circulating BRAF V600E and miRNAs. Although promising, use of these markers needs to be refined by the technical sight, and the actual prognostic value is still yet to be validated. © 2016 Society for Endocrinology.

Prognostic Value of MicroRNAs in Coronary Artery Diseases: A Meta-Analysis.

PubMed

Kim, Ji Suk; Pak, Kyoungjune; Goh, Tae Sik; Jeong, Dae Cheon; Han, Myoung Eun; Kim, Jihyun; Oh, Sae Ock; Kim, Chi Dae; Kim, Yun Hak

2018-06-01

Coronary artery diseases (CADs) are the leading causes of death in the world. Recent studies have reported that differentially expressed microRNAs (miRNAs) are associated with prognosis or major adverse cardiac events (MACEs) in CAD patients. In a previous meta-analysis, the authors made serious mistakes that we aimed to correct through an updated systematic review and meta-analysis of the prognostic value of altered miRNAs in patients with CADs. We performed a systematic search of MEDLINE (from inception to May 2017) and EMBASE (from inception to May 2017) for English-language publications. Studies of CADs with results on miRNAs that reported survival data or MACEs were included. Data were extracted from each publication independently by two reviewers. After reviewing 515 articles, a total eight studies were included in this study. We measured pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of miRNA 133a with a fixed-effect model (pooled HR, 2.35; 95% CI, 1.56-3.55). High expression of miRNA 133a, 208b, 126, 197, 223, and 122-5p were associated with high mortality. Additionally, high levels of miRNA 208b, 499-5p, 134, 328, and 34a were related with MACEs. The present study confirmed that miRNA 133a, which was associated with high mortality in CAD patients, holds prognostic value in CAD. More importantly, this study corrected issues raised against a prior meta-analysis and provides accurate information. © Copyright: Yonsei University College of Medicine 2018.

Parotid metastasis--an independent prognostic factor for head and neck cutaneous squamous cell carcinoma.

PubMed

Ch'ng, S; Maitra, A; Lea, R; Brasch, H; Tan, S T

2006-01-01

of 18 months, the loco-regional recurrence rate was 52%. The presence of parotid disease was an independent prognostic factor on survival (p < 0.01), and P3 fared significantly worse than P1 and P2. Those patients who had both parotid and neck disease fared worse than those who had parotid or neck disease alone (p = 0.01). N2 had a significantly poorer outcome compared with N1 (p < 0.01). Immunosuppression (p = 0.01) and a positive surgical margin (p < 0.01) were significant adverse prognostic factors for survival. Adjuvant radiotherapy, extracapsular spread, and perineural and vascular invasion did not influence survival. Our study demonstrates that the extent of parotid disease is an independent prognostic factor for metastatic head and neck cutaneous SCC.

Adverse life events in elderly patients with major depression or dysthymic disorder and in healthy-control subjects.

PubMed

Devanand, D P; Kim, Min Kyung; Paykina, Natalya; Sackeim, Harold A

2002-01-01

The authors compared elderly outpatients (> or =60 years) with major depression or dysthymic disorder and healthy-control subjects on the type and subjective impact of adverse life events. The Geriatric Adverse Life Events Scale (GALES) was developed for this purpose. Fifty patients with major depression, 79 patients with dysthymic disorder, and 40 healthy controls completed the GALES. Adverse life events during two time periods were assessed: the year before the evaluation, and the year before onset of the index episode (patients only). During the year before evaluation, patients with major depression reported more life events with greater negative impact, particularly for interpersonal conflicts, and dysthymic patients scored intermediate between patients and controls. Sum scores for perceived stress and negative impact on mood differed significantly among the groups: highest for major depression, intermediate for dysthymic disorder, and lowest for controls. During the year before onset, patients with major depression reported significantly higher sum scores for negative impact on mood than patients with dysthymic disorder. On several measures, patients with major depression perceived greater negative impact of life events than patients with dysthymic disorder and healthy controls, particularly for interpersonal conflicts. The subjective impact of adverse life events may play an important role in the expression of depressive illness in elderly patients, particularly in major depression, and it needs to be considered in clinical management.

Methodology for computing the burden of disease of adverse events following immunization.

PubMed

McDonald, Scott A; Nijsten, Danielle; Bollaerts, Kaatje; Bauwens, Jorgen; Praet, Nicolas; van der Sande, Marianne; Bauchau, Vincent; de Smedt, Tom; Sturkenboom, Miriam; Hahné, Susan

2018-03-24

Composite disease burden measures such as disability-adjusted life-years (DALY) have been widely used to quantify the population-level health impact of disease or injury, but application has been limited for the estimation of the burden of adverse events following immunization. Our objective was to assess the feasibility of adapting the DALY approach for estimating adverse event burden. We developed a practical methodological framework, explicitly describing all steps involved: acquisition of relative or absolute risks and background event incidence rates, selection of disability weights and durations, and computation of the years lived with disability (YLD) measure, with appropriate estimation of uncertainty. We present a worked example, in which YLD is computed for 3 recognized adverse reactions following 3 childhood vaccination types, based on background incidence rates and relative/absolute risks retrieved from the literature. YLD provided extra insight into the health impact of an adverse event over presentation of incidence rates only, as severity and duration are additionally incorporated. As well as providing guidance for the deployment of DALY methodology in the context of adverse events associated with vaccination, we also identified where data limitations potentially occur. Burden of disease methodology can be applied to estimate the health burden of adverse events following vaccination in a systematic way. As with all burden of disease studies, interpretation of the estimates must consider the quality and accuracy of the data sources contributing to the DALY computation. © 2018 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Accelerated Aging with Electrical Overstress and Prognostics for Power MOSFETs

NASA Technical Reports Server (NTRS)

Saha, Sankalita; Celaya, Jose Ramon; Vashchenko, Vladislav; Mahiuddin, Shompa; Goebel, Kai F.

2011-01-01

Power electronics play an increasingly important role in energy applications as part of their power converter circuits. Understanding the behavior of these devices, especially their failure modes as they age with nominal usage or sudden fault development is critical in ensuring efficiency. In this paper, a prognostics based health management of power MOSFETs undergoing accelerated aging through electrical overstress at the gate area is presented. Details of the accelerated aging methodology, modeling of the degradation process of the device and prognostics algorithm for prediction of the future state of health of the device are presented. Experiments with multiple devices demonstrate the performance of the model and the prognostics algorithm as well as the scope of application. Index Terms Power MOSFET, accelerated aging, prognostics

Childhood Adversity, Religion, and Change in Adult Mental Health.

PubMed

Jung, Jong Hyun

2018-02-01

Research indicates that childhood adversity is associated with poor mental health in adulthood. The purpose of this study is to examine whether the deleterious long-term effects of childhood adversity on adult mental health are reduced for individuals who are involved in religious practices. Using longitudinal data from a representative sample of American adults ( N = 1,635), I find that religious salience and spirituality buffer the noxious effects of childhood abuse on change in positive affect over time. By contrast, these stress-buffering properties of religion fail to emerge when negative affect serves as the outcome measure. These results underscore the importance of religion as a countervailing mechanism that blunts the negative impact of childhood abuse on adult mental health over time. I discuss the theoretical implications of these findings for views about religion, childhood adversity, and mental health.