976 resultados para Phase-i-ii
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Potilaiden käsitys terveyteen liittyvästä elämänlaadusta lonkan tekonivelleikkauksen jälkeisenä toipumisaikana – kuuden kuukauden seurantatutkimus Tässä kaksivaiheisessa seurantatutkimuksessa tarkasteltiin potilaiden käsitystä terveyteen liittyvästä elämänlaadusta lonkan tekonivelleikkauksen jälkeisenä toipumisaikana. Tutkimuksen ensimmäisessä vaiheessa tarkoituksena oli sekä kuvailla potilaiden kokemuksia potilaana olosta, saamastaan hoidosta ja terveyspalveluorganisaatiosta että analysoida aikaisempien tutkimusten perusteella leikkauksen tuloksia potilaan kannalta. Toisessa vaiheessa tarkoituksena oli arvioida potilaiden kokemaa elämänlaatua leikkauksen jälkeen, ja sitä vaikuttivatko primaaritulokset (fyysinen toimintakyky, kipu, ahdistus) tai taloudelliset seuraukset (potilaiden itsensämaksamat kustannukset, palvelujen käyttö) terveyteen liittyvään elämänlaatuun. Tutkimuksen tavoitteena oli löytää mahdolliset kriittiset ajankohdat tai tekijät, jotka saattavat hidastaa toipumista ja siten huonontaa potilaiden elämänlaatua. Tätä tietoa voidaan käyttää hoitotyössä kun suunnitellaan sopivaa hoitoa ja tukea toipumisajalle. Tutkimuksen ensimmäisessä vaiheessa primaarileikkaukseen tulevat potilaat (n = 17) kuvailivat teemahaastatteluissa kokemuksiaan kahdesti leikkauksen jälkeen. Haastatteluaineisto analysoitiin induktiivisella sisällönanalyysilla. Lisäksi 17 tutkimusartikkelista analysoitiin deduktiivisella sisällönanalyysilla leikkauksen tuloksia potilaalle, tuloksiin vaikuttavia tekijöitä ja käytetyt tutkimusmetodit. Toisessa vaiheessa primaari- tai revisioleikkaukseen tulevat potilaat (n = 100) arvioivat leikkauksen tuloksia kuuden kuukauden ajan leikkauksen jälkeen: terveyteen liittyvää elämänlaatua, primaarituloksia ja taloudellisia seurauksia. Aineisto kerättiin erilaisilla mittareilla: Sickness Impact Profile, Finnish Version, Stait-Trait Anxiety Inventory, ja Numeric Rating Scale. Lisäksi käytettiin tätä tutkimusta varten tehtyjä kyselylomakkeita: Fyysinen toimintakyky-mittari, Palvelujen käyttö-mittari ja Kustannusmittari. Tutkimuksen toiseen vaiheen tulokset analysoitiin tilastollisilla menetelmillä. Potilaiden terveyteen liittyvä elämänlaatu parani ja kipu lievittyi leikkauksen jälkeen ja fyysinen toimintakyky lisääntyi toipumisaikana. Positiivisista muutoksista huolimatta potilaat kokivat ahdistusta samassa määrin kuin ennen leikkaustakin. Palvelujen käyttö vaihteli toipumisajan kuluessa ja potilaiden maksamissa kustannuksissa oli suuria vaihteluita. Fyysisen toimintakyvyn lisääntyminen ja kivun lieveneminen paransivat terveyteen liittyvää elämänlaatua. Sen sijaan huonompi elämänlaatu toipumisaikana oli yhteydessä suurempaan palvelujen käyttöön, kun taas kustannuksilla ei ollut yhteyttä elämänlaatuun. Potilaiden ominaispiirteet tulisi ottaa enemmän huomioon suunniteltaessa sopivaa leikkauksenjälkeistä hoitoa ja tukea. Potilaat tarvitsevat yksilöllisiä ohjeita, sillä monet taustatekijät (esim. ikä, sukupuoli, preoperatiivinen kipu, siviilisääty, ja leikkaustyyppi) vaikuttavat toipumiseen.
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Cilengitide, a cyclicized arginine-glycine-aspartic acid-containing pentapeptide, potently blocks ανβ3 and ανβ5 integrin activation. Integrins are upregulated in many malignancies and mediate a wide variety of tumor-stroma interactions. Cilengitide and other integrin-targeting therapeutics have preclinical activity against many cancer subtypes including glioblastoma (GBM), the most common and deadliest CNS tumor. Cilengitide is active against orthotopic GBM xenografts and can augment radiotherapy and chemotherapy in these models. In Phase I and II GBM trials, cilengitide and the combination of cilengitide with standard temozolomide and radiation demonstrate consistent antitumor activity and a favorable safety profile. Cilengitide is currently under evaluation in a pivotal, randomized Phase III study (Cilengitide in Combination With Temozolomide and Radiotherapy in Newly Diagnosed Glioblastoma Phase III Randomized Clinical Trial [CENTRIC]) for newly diagnosed GBM. In addition, randomized controlled Phase II studies with cilengitide are ongoing for non-small-cell lung cancer and squamous cell carcinoma of the head and neck. Cilengitide is the first integrin inhibitor in clinical Phase III development for oncology.
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The Office of Special Investigations at Iowa Department of Transportation (DOT) collects FWD data on regular basis to evaluate pavement structural conditions. The primary objective of this study was to develop a fully-automated software system for rapid processing of the FWD data along with a user manual. The software system automatically reads the FWD raw data collected by the JILS-20 type FWD machine that Iowa DOT owns, processes and analyzes the collected data with the rapid prediction algorithms developed during the phase I study. This system smoothly integrates the FWD data analysis algorithms and the computer program being used to collect the pavement deflection data. This system can be used to assess pavement condition, estimate remaining pavement life, and eventually help assess pavement rehabilitation strategies by the Iowa DOT pavement management team. This report describes the developed software in detail and can also be used as a user-manual for conducting simulation studies and detailed analyses. *********************** Large File ***********************
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Phase II of this study further evaluated the performance of plant-produced warm-mix asphalt (WMA) mixes by conducting additional mixture performance tests at a broader range of temperatures, adding additional pavements to the study, comparing virgin and recovered binder properties, performing pavement condition surveys, and comparing survey data with the Mechanistic Empirical Pavement Design Guide (MEPDG) forecast for pavement damage over 20 years of service life. Further objectives detailing curing behavior, quality assurance testing, and hybrid technologies were as follows: * Compare the predicted and observed field performance of existing WMA trials produced in the previous Phase I study to that of hot-mix asphalt (HMA) control sections to determine if Phase I conclusions are translating to the field; * Identify any curing effect (and timing of the effect) of WMA mixtures and binders in the field; * Determine how the field-compacted mixture properties and recovered binder properties of WMA compare to those of HMA over time for technologies common to Iowa; * Identify the protocols for WMA sample preparation for volumetric and performance testing that best simulate field conditions. The findings of this study indicate that WMA additives do show statistical differences in mixture properties in some of the mixes tested. These differences will not always be statistically different from mixture to mixture. Multiple factors, such as WMA additive type, amount of recycled asphalt material, construction conditions, and mixture variability all play a role in determining the extent of which WMA and HMA mixes differ. Other significant findings of this study include effects of curing, aging in recovered binders from HMA and WMA cores, and the influence of recycled asphalt shingles (RAS) used with WMA. These findings will be of interest to owner agencies and contractors utilizing WMA technologies.
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BACKGROUND: Evaluation of syncope remains often unstructured. The aim of the study was to assess the effectiveness of a standardized protocol designed to improve the diagnosis of syncope. METHODS: Consecutive patients with syncope presenting to the emergency departments of two primary and tertiary care hospitals over a period of 18 months underwent a two-phase evaluation including: 1) noninvasive assessment (phase I); and 2) specialized tests (phase II), if syncope remained unexplained after phase I. During phase II, the evaluation strategy was alternately left to physicians in charge of patients (control), or guided by a standardized protocol relying on cardiac status and frequency of events (intervention). The primary outcomes were the diagnostic yield of each phase, and the impact of the intervention (phase II) measured by multivariable analysis. RESULTS: Among 1725 patients with syncope, 1579 (92%) entered phase I which permitted to establish a diagnosis in 1061 (67%) of them, including mainly reflex causes and orthostatic hypotension. Five-hundred-eighteen patients (33%) were considered as having unexplained syncope and 363 (70%) entered phase II. A cause for syncope was found in 67 (38%) of 174 patients during intervention periods, compared to 18 (9%) of 189 during control (p<0.001). Compared to control periods, intervention permitted diagnosing more cardiac (8%, vs 3%, p=0.04) and reflex syncope (25% vs 6%, p<0.001), and increased the odds of identifying a cause for syncope by a factor of 4.5 (95% CI: 2.6-8.7, p<0.001). Overall, adding the diagnostic yield obtained during phase I and phase II (intervention periods) permitted establishing the cause of syncope in 76% of patients. CONCLUSION: Application of a standardized diagnostic protocol in patients with syncope improved the likelihood of identifying a cause for this symptom. Future trials should assess the efficacy of diagnosis-specific therapy.
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The Phase I research, Iowa Department of Transportation (IDOT) Project HR-214, "Feasibility Study of Strengthening Existing Single Span Steel Beam Concrete Deck Bridges," verified that post-tensioning can be used to provide strengthening of the composite bridges under investigation. Phase II research, reported here, involved the strengthening of two full-scale prototype bridges - one a prototype of the model bridge tested during Phase I and the other larger and skewed. In addition to the field work, Phase II also involved a considerable amount of laboratory work. A literature search revealed that only minimal data existed on the angle-plus-bar shear connectors. Thus, several specimens utilizing angle-plus-bar, as well as channels, studs and high strength bolts as shear connectors were fabricated and tested. To obtain additional shear connector information, the bridge model of Phase I was sawed into four composite concrete slab and steel beam specimens. Two of the resulting specimens were tested with the original shear connection, while the other two specimens had additional shear connectors added before testing. Although orthotropic plate theory was shown in Phase I to predict vertical load distribution in bridge decks and to predict approximate distribution of post-tensioning for right-angle bridges, it was questioned whether the theory could also be used on skewed bridges. Thus, a small plexiglas model was constructed and used in vertical load distribution tests and post-tensioning force distribution tests for verification of the theory. Conclusions of this research are as follows: (1) The capacity of existing shear connectors must be checked as part of a bridge strengthening program. Determination of the concrete deck strength in advance of bridge strengthening is also recommended. (2) The ultimate capacity of angle-plus-bar shear connectors can be computed on the basis of a modified AASHTO channel connector formula and an angle-to-beam weld capacity check. (3) Existing shear connector capacity can be augmented by means of double-nut high strength bolt connectors. (4) Post-tensioning did not significantly affect truck load distribution for right angle or skewed bridges. (5) Approximate post-tensioning and truck load distribution for actual bridges can be predicted by orthotropic plate theory for vertical load; however, the agreement between actual distribution and theoretical distribution is not as close as that measured for the laboratory model in Phase I. (6) The right angle bridge exhibited considerable end restraint at what would be assumed to be simple support. The construction details at bridge abutments seem to be the reason for the restraint. (7) The skewed bridge exhibited more end restraint than the right angle bridge. Both skew effects and construction details at the abutments accounted for the restraint. (8) End restraint in the right angle and skewed bridges reduced tension strains in the steel bridge beams due to truck loading, but also reduced the compression strains caused by post-tensioning.
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This report describes the continuation of the development of performance measures for the Iowa Department of Transportation (DOT) Offices of Construction. Those offices are responsible for administering transportation construction projects for the Iowa DOT. Researchers worked closely with the Benchmark Steering Team which was formed during Phase I of this project and is composed of representatives of the Offices of Construction. The research team conducted a second survey of Offices of Construction personnel, interviewed numerous members of the Offices and continued to work to improve the eight key processes identified during Phase I of this research. The eight key processes include Inspection of Work, Resolution of Technical Issues, Documentation of Work Progress and Pay Quantities, Employee Training and Development, Continuous Feedback for Improved Contract Documents, Provide Safe Traffic Control, External/Public Communication, and Providing Pre-Letting Information. Three to four measurements were specified for each key process. Many of these measurements required opinion surveys of employees, contractors, and others. During Phase II, researchers concentrated on conducting surveys, interviewing respondents to improve future surveys, and facilitating Benchmark Steering Team monthly meetings. Much effort was placed on using the information collected during the first year's research to improve the effectiveness and efficiency of the Offices of Construction. The results from Process Improvement Teams that studied Traffic Control and Resolution of Technical Issues were used to improve operations.
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Examination of field portland cement concrete cores, from Iowa pavements with premature deterioration, reveals extensive infilling of calcium sulfate aluminum (CSA) compound in their air voids. A previous study (Phase I) has shown some evidence of the correlation between freeze-thaw durability of concretes and ettringite infilling. To further verify the previous observation, a more extensive experimental program was conducted in this Phase 2 study. A total of 101 concrete mixes were examined. Seven cements, six fly ashes, two water reducers and three coarse aggregates were used in the concrete mixes. Specimens were under moist curing for up to 223 days before being subjected to the freeze-thaw cycling. An environmental treatment consisting of three consecutive wet [70 deg F (21 deg C) in distilled water]/dry [120 deg F (49 deg C) in oven] cycles was applied to some specimens. Immediately prior to the freeze-thaw cycling, most specimens were examined by a low-vacuum scanning electron microscope (SEM) for their microstructure. The results obtained further demonstrate the correlation between concrete freeze-thaw response and CSA compound infilling in the air voids. The extent of the infilling depends on the period of moist curing as well as the wet/dry treatment. The extent of the infilling also relates to materials used. Concrete mixes with extensive infilling are more vulnerable to the freeze-thaw attack. Based on the obtained results, material criteria on cements and fly ashes for mainline paving were proposed for minimizing potential infilling of CSA compound in concrete.
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Traffic noise monitoring using FHWA's Demonstration Projects Division Mobile Noise Laboratory at free field, single wall and parallel barrier site on I-380 in Evansdale, Iowa is described. Access to I-380 prior to its being open to traffic afforded a controlled pass-by monitoring phase involving different vehicle types. A subsequent second phase entailed identical measurement methodology to monitor "real world" I-380 traffic noise. Phase I data indicated increases in noise were significant under the parallel barrier conditions for light duty vehicles operating in the far lane. Phase II results showed that the actual I-380 traffic mix largely offset the earlier observed effect, but minor increases in traffic noise under the parallel system were noted. These differences in noise barrier system effectiveness are judged to be insignificant at this particular study location.
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INTRODUCTION: Video records are widely used to analyze performance in alpine skiing at professional or amateur level. Parts of these analyses require the labeling of some movements (i.e. determining when specific events occur). If differences among coaches and differences for the same coach between different dates are expected, they have never been quantified. Moreover, knowing these differences is essential to determine which parameters reliable should be used. This study aimed to quantify the precision and the repeatability for alpine skiing coaches of various levels, as it is done in other fields (Koo et al, 2005). METHODS: A software similar to commercialized products was designed to allow video analyses. 15 coaches divided into 3 groups (5 amateur coaches (G1), 5 professional instructors (G2) and 5 semi-professional coaches (G3)) were enrolled. They were asked to label 15 timing parameters (TP) according to the Swiss ski manual (Terribilini et al, 2001) for each curve. TP included phases (initiation, steering I-II), body and ski movements (e.g. rotation, weighting, extension, balance). Three video sequences sampled at 25 Hz were used and one curve per video was labeled. The first video was used to familiarize the analyzer to the software. The two other videos, corresponding to slalom and giant slalom, were considered for the analysis. G1 realized twice the analysis (A1 and A2) at different dates and TP were randomized between both analyses. Reference TP were considered as the median of G2 and G3 at A1. The precision was defined as the RMS difference between individual TP and reference TP, whereas the repeatability was calculated as the RMS difference between individual TP at A1 and at A2. RESULTS AND DISCUSSION: For G1, G2 and G3, a precision of +/-5.6 frames, +/-3.0 and +/-2.0 frames, was respectively obtained. These results showed that G2 was more precise than G1, and G3 more precise than G2, were in accordance with group levels. The repeatability for G1 was +/-3.1 frames. Furthermore, differences among TP precision were observed, considering G2 and G3, with largest differences of +/-5.9 frames for "body counter rotation movement in steering phase II", and of 0.8 frame for "ski unweighting in initiation phase". CONCLUSION: This study quantified coach ability to label video in term of precision and repeatability. The best precision was obtained for G3 and was of +/-0.08s, which corresponds to +/-6.5% of the curve cycle. Regarding the repeatability, we obtained a result of +/-0.12s for G1, corresponding to +/-12% of the curve cycle. The repeatability of G2 and G3 are expected to be lower than the precision of G1 and the corresponding repeatability will be assessed soon. In conclusion, our results indicate that the labeling of video records is reliable for some TP, whereas caution is required for others. REFERENCES Koo S, Gold MD, Andriacchi TP. (2005). Osteoarthritis, 13, 782-789. Terribilini M, et al. (2001). Swiss Ski manual, 29-46. IASS, Lucerne.
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A large variety of cancer vaccines have undergone extensive testing in early-phase clinical trials. A limited number have also been tested in randomized phase II clinical trials. Encouraging trends toward increased survival in the vaccine arms have been recently observed for 2 vaccine candidates in patients with non-small-cell lung cancer. These have provided the impetus for the initiation of phase III trials in large groups of patients with lung cancer. These vaccines target 2 antigens widely expressed in lung carcinomas: melanoma-associated antigen 3, a cancer testis antigen; and mucin 1, an antigen overexpressed in a largely deglycosylated form in advanced tumors. Therapeutic cancer vaccines aim at inducing strong CD8 and CD4 T-cell responses. The majority of vaccines recently tested in phase I clinical trials show efficacy in terms of induction of specific tumor antigen immunity. However, clinical efficacy remains to be determined but appears limited. Efforts are thus aimed at understanding the basis for this apparent lack of effect on tumors. Two major factors are involved. On one hand, current vaccines are suboptimal. Strong adjuvant agents and appropriate tumor antigens are needed. Moreover, dose, route, and schedule also need optimization. On the other hand, it is now clear that large tumors often present a tolerogenic microenvironment that hampers effective antitumor immunity. The partial understanding of the molecular pathways leading to functional inactivation of T cells at tumor sites has provided new targets for intervention. In this regard, blockade of cytotoxic T-lymphocyte antigen-4 and programmed death-1 with humanized monoclonal antibodies has reached the clinical testing stage. In the future, more potent cancer vaccines will benefit from intense research in antigen discovery and adjuvant agents. Furthermore, it is likely that vaccines need to be combined with compounds that reverse major tolerogenic pathways that are constitutively active at the tumor site. Developing these combined approaches to vaccination in cancer promises new, exciting findings and, at the same time, poses important challenges to academic research institutions and the pharmaceutical industry.
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Objective: To assess the safety/tolerability of the combination lapatinib (L) and docetaxel (D) in patients with Her 2/neu overexpressing breast cancer (BC). This study is important as it will define how to deliver lapatinib with taxotere, a highly active drug in breast cancer. Patients and Methods: Female patients (pts) with locally advanced, inflammatory or large operable BC were treated with escalating doses of L from 1000 to 1250 mg/day, in combination with D given IV every 21 days at doses ranging from 75 to 100 mg/m2 for 4 cycles. At least 3 pts were treated at each dose level. The definition of dose limiting toxicity (DLT) is based on the toxicity assessed at cycle 1 as follows: any grade 3−4 non hematological toxicity, ANC < 0.5 G/L lasting for 7 days or more, febrile neutropenia or thrombocytopenia <25 G/L. GCSF was not permitted as primary prophylaxis. Core biopsies were mandatory at baseline and after cycle 4. Pharmcokinetic (PK) samples were collected on day 1 of cycles 1 and 2. Results: To date, 18 pts with a median age of 53 years (range 36−65) have been enrolled at 5 Dose Levels (DLs). The toxicity profile for 18 patients (68 documented cycles) is summarized below. At DL5 (1000/100), 2 pts had DLTs (neutropenia grade 4 _7 days and febrile neutropenia), and 3 additional pts were enrolled with primary prophylactic G-CSF. As expected, the safety profile improved and the dose escalation will continue with prophylactic G-CSF to investigate DL6 (1250/100). These findings are consistent with published Phase I data for this combination [1]. N= 18 patients n (%) Grade 1 Grade 2 Grade 3 Grade 4 neutropenia 1 (6) 3 (17) 13 (72) febrile neutropenia 2 (11) fatigue 8 (44) 7 (39) diarrhoea 9 (50) 3 (17) pain: joint/muscle/other 5 (28)/4 (22)/3 (17) 4 (22)/4 (22)/3 (17) 0/0/1 (6) constipation 2 (11) 3 (17) 1 (6) elevated transaminases SGPT/SGOT 7 (39)/5 (28) Conclusions: The main toxicity of the L + D combination is haematological and was reached at DL5 (1000/100), without primary GCSF. An additional DL6 with primary prophylactic GCSF is being investigated (1250/100). PK data will be presented at the meeting plus the recommended dose for phase II studies.
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Background: The first AO comprehensive pediatric long bone fracture classification system has been established following a structured path of development and validation with experienced pediatric surgeons. Methods: A follow-up series of agreement studies was applied to specify and evaluate a grading system for displacement of pediatric supracondylar fractures. An iterative process comprising an international group of 5 experienced pediatric surgeons (Phase 1) followed by a pragmatic multicenter agreement study involving 26 raters (Phase 2) was used. The last evaluations were conducted on a consecutive collection of 154 supracondylar fractures documented by standard anteroposterior and lateral radiographs. Results: Fractures were classified according to 1 of 4 grades: I = incomplete fracture with no or minimal displacement; II = Incomplete fracture with continuity of the posterior (extension fracture) or anterior cortex (flexion fracture); III = lack of bone continuity (broken cortex), but still some contact between the fracture planes; IV = complete fracture with no bone continuity (broken cortex), and no contact between the fracture planes. A diagnostic algorithm to support the practical application of the grading system in a clinical setting, as well as an aid using a circle placed over the capitellum was proposed. The overall kappa coefficients were 0.68 and 0.61 in the Phase 1 and Phase 2 studies, respectively. In the Phase 1 study, fracture grades I, II, III, and IV were classified with median accuracies of 91%, 82%, 83%, and 99.5%, respectively. Similar median accuracies of 86% (Grade I), 73% (Grade II), 83%(Grade III), and 92% were reported for the Phase 2 study. Reliability was high in distinguishing complete, unstable fractures from stable injuries [ie, kappa coefficients of 0.84 (Phase 1) and 0.83 (Phase 2) were calculated]; in Phase 2, surgeons' accuracies in classifying complete fractures were all above 85%. Conclusions: With clear and unambiguous definition, this new grading system for supracondylar fracture displacement has proved to be sufficiently reliable and accurate when applied by pediatric surgeons in the framework of clinical routine as well as research.
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BACKGROUND: Prognostic models and nomograms were recently developed to predict survival of patients with newly diagnosed glioblastoma multiforme (GBM).1 To improve predictions, models should be updated with the most recent patient and disease information. Nomograms predicting patient outcome at the time of disease progression are required. METHODS: Baseline information from 299 patients with recurrent GBM recruited in 8 phase I or II trials of the EORTC Brain Tumor Group was used to evaluate clinical parameters as prognosticators of patient outcome. Univariate (log rank) and multivariate (Cox models) analyses were made to assess the ability of patients' characteristics (age, sex, performance status [WHO PS], and MRC neurological deficit scale), disease history (prior treatments, time since last treatment or initial diagnosis, and administration of steroids or antiepileptics) and disease characteristics (tumor size and number of lesions) to predict progression free survival (PFS) and overall survival (OS). Bootstrap technique was used for models internal validation. Nomograms were computed to provide individual patients predictions. RESULTS: Poor PS and more than 1 lesion had a significant prognostic impact for both PFS and OS. Antiepileptic drug use was significantly associated with worse PFS. Larger tumors (split by the median of the largest tumor diameter >42.5 mm) and steroid use had shorter OS. Age, sex, neurologic deficit, prior therapies, and time since last therapy or initial diagnosis did not show independent prognostic value for PFS or OS. CONCLUSIONS: This analysis confirms that PS but not age is a major prognostic factor for PFS and OS. Multiple or large tumors and the need to administer steroids significantly increase the risk of progression and death. Nomograms at the recurrence could be used to obtain accurate predictions for the design of new targeted therapy trials or retrospective analyses. (1. T. Gorlia et al., Nomograms for predicting survival of patients with newly diagnosed glioblastoma. Lancet Oncol 9 (1): 29-38, 2008.)