<p>Uvod: Iz rezultata brojnih randomiziranih kliničkih studija proizi&scaron;le su smernice u koijma se navodi da je upotreba neinvazivne ventilacije (NIV), uz farmakolo&scaron;ku terapiju, indikovana kod svih bolesnika sa te&scaron;kom egzacerbacijom hronične opstruktivne bolesti pluća (HOBP), i to sa najvi&scaron;im nivoom preporuke. Dokazano je da se upotrebom NIV-a smanjuje broj intubacija, uz smanjenje mortaliteta ali i skraćenje dužine bolničkog lečenja. S obzirom da je nekada ventilatorna potpora bila pružana isključivo u jedinicama intenzivne nege, a da je kapacitet ovakvih odeljenja gotovo stalno popunjen, postavlja se pitanje adekvatnog okruženja unutar bolnice gde se bezbedno i efikasno može primeniti neinvazivna ventilacija, ali gde se i na vreme mogu prepoznati rani znakovi njene neuspe&scaron;ne primene, nakon čega trebaobezbediti pravovremenu endotrahealnu intubaciju. Stoga su rađene brojne studije u cilju izdvajanja ranih prediktora ishoda neinvazivne ventilacije - kako u cilju ranog prepoznavanja neuspeha NIV-a i omogućavanja pravovremene intubacije, tako i u cilju stratifikacije pacijenata sa različitim stepenom rizika za neuspeh, uz obezbeđivanje adekvatnog nivoa nege i monitoringa za sve bolesnike. Ciljevi: Ciljevi istraživanja su da se utvrdi koji pokazatelji koreliraju sa neuspe&scaron;nim ishodom primene neinvazivne mehaničke ventilacije kod bolesnika sa te&scaron;kom egzacerbacijom hronične opstruktivne bolesti pluća, kako bi se kreirao prognostički model ishoda lečenja, te da se se na osnovu prognostičkog modela stratifikuju bolesnici prema stepenu rizika za neuspeh NIV-a i u skladu sa njim predloži adekvatan stepen monitoringa, odnosno kliničko okruženje za bezbedno i efikasno pružanje ventilatorne potpore. Metodologija: U Institutu za plućne bolesti Vojvodine u Sremskoj Kamenici sprovedeno je prospektivno opservaciono istraživanje u trajanju od 39 meseci, u koje je uključeno 250 konsekutivnih bolesnika hospitalizovanih zbog te&scaron;ke egzacerbacije HOBP-a sa respiratornom acidozom. NIV je primenjen u modu pritiskom podržane ventilacije ventilatorima marke Covidien tipa Airox Supportair, uz upotrebu oronazalne maske. Početni parametri su podrazumevali upotrebu ekspiratornog pozitivnog pritiska u disajnim putevima - EPAP-a od 5 cm H2O i inspiratornog pozitivnog pritiska u disajnim putevima IPAPa od 12 cm H20, koji su u potom titrirani ka ciljnim vrednostima IPAPa od 15-20 cmH2O, a u skladu sa kliničkim odgovorom. Za svakog bolesnika evidentirani su: pol, starost, ranija primena dugotrajne oksigenoterapije u kućnim uslovima, primena NIV-a tokom prethodnih hospitalizacija, komorbiditeti preko Charlson indeksa, vreme proteklo od početka hospitalizacije do započinjanja NIV-a, vrednosti pH, bikarbonata, PaCO2 i PaO2 u gasnim analizama arterijske krvi pre započinjanja NIV-a, inicijalna SpO2 i odnos PaO2/FiO2, zatim promena vrednosti pH, PaCO2 i PaO2 u gasnim analizama arterijske krvi sat vremena nakon početka primene NIV-a, inicijalni vitalni parametri - srčana frekvenca, respiratorna frekvenca, stanje svesti procenjeno Glazgov koma skalom (GCS), telesna temperatura, sistolni arterijski pritisak, diureza, a potom zbirni modifikovani ranoupozoravajući bodovni skor (MEWS-modified early warning score), prisustvo i opseg konsolidacija na radiogramu grudnog ko&scaron;a, saradnja bolesnika, te mesto primene NIV-a. Kao primarni ishod istraživanja definisan je neuspeh neinvazivne mehaničke ventilacije: intubacija ili smrtni ishod u toku hospitalizacije uzrokovan respiratornom insuficijencijom. Svaki potencijalni prediktor neuspeha je prvo evaluiran uz pomoć univarijantne analize, a potom su svi faktori rizika za koje je univarijantnom analizom utvrdjena statistička značajnost analizirani uz pomoć multivarijantne logističke regresije, u cilju utvrdjivanja adekvatnih statističkih modela. Rezultati: Od ukupno 250 bolesnika NIV je uspe&scaron;no primenjen kod 164 bolesnika (65.6%). Ukupno 139 (59.3%) bolesnika bilo je mu&scaron;kog pola, a prosečna starost svih ispitanika bila je 67 godina. Bolesnici sa neuspe&scaron;nim ishodom NIV-a imaju, prema univarijantnoj analizi: statistički značajno veće vrednosti Charlson indexa (p=0.002, OR 1.293, 95%CI 1.103-1.516), konsolidacije u &ge;2 kvadranata (p=0.000, OR 5.384, 95%CI 2.487-11.655), duže vreme od početka hospitalizacije do započinjanja NIV-a (p=0.0034, OR 1.005, 95%CI 1.000-1.009), tahikardiju (p=0.031, OR 2.292, 95%CI 1.080-4.864), vrednost GCS &le;11 (p=0.042, OR 1.000, 95%CI 0.165-0.969), veći MEWS skor (p=0.000, OR 1.708, 95%CI 1.410-2.068), niže vrednosti inicijalnog pH (p=0.004, OR 0.002, 95%CI 0.000-0.147), slabiju saradnju (p=0.000, OR 2.102, 95%CI 0.145-0.339). Mesto gde je sprovedena NIV je značajno uticalo na ishod &ndash; &scaron;anse za neuspe&scaron;an ishod su bile dvostruko veće kod bolesnika ventiliranih na op&scaron;tem odeljenju (p=0.006, OR 2.102, 95%CI 1.236-3.574). Kao nezavisni prediktori neuspeha nakon multivarijantne logističke regresije pokazali su se vrednosti Charlson-ovog indexa (p=0.043, OR 1.246, 95%CI 1.007-1.541), MEWS skora (p=0.010, OR 1.394, 95%CI 1.083-1.795), inicijalne vrednosti pH (p=0.030, OR 0.642, 95%CI 0.430-0.958) i stepena saradnje (p=0.000, OR 0.230, 95%CI 0.141-0.376). Zaključci: Bolesnici sa visokim vrednostima Charlson-ovog indeksa (preko 6 bodova) i MEWS-ovog skora (preko 4 boda), te niskom inicijalnom pH vredno&scaron;ću arterijske krvi (ispod 7.29) i niskim stepenom saradnje (manjim od 4) su bolesnici koji imaju povi&scaron;en stepen rizika za neuspe&scaron;an ishod primene neinvazivne ventilacije. Bolesnici visokog stepena rizika treba da se zbrinjavaju i neinvazivno ventiliraju na odeljenjima poluintenzivne i intenzivne nege, dok se bolesnici sa manjim stepenom rizika mogu inicijalno neinvazivno ventilirati i na op&scaron;tim odeljenjima, uz adekvatan monitoring i nadzor obučenog osoblja.</p> / <p>Introduction: Clinical guidelines that have evolved from the results of numerous randomized clinical trials state that the use of non-invasive ventilation (NIV), in addition to pharmacological therapy, is necessary in all patients wih severe exacerbation of chronic obstructive pulmonary disease (COPD) - at the highest level of recommendation. It has been proven that the use of NIV leeds to reduction in mortality, intubation rates, and the length of stay in hospitals. Since ventilatory support in past was only delivered in intensive care units, and bearing in mind that their capacities are limited, there is a question of an adequate setting within a hospital where NIV can be used safely and efficiently, and where potential early signs of failure will be timely recognized and patient intubated, if necessary. Consequently, the studies were performed in order to identify early predictors of NIV outcome &ndash; in order to recognize NIV failure and necessity for transition towards invasive ventilation, but also in order to stratify the patients according to the level of risk, which will then dictate the necessary level of care and monitoring. Goals: This research is aimed at identification of parameters that correlate with failure of non-invasive ventilation in patients with severe exacerbation of COPD, in order to create prognostic model of outcome, which will then enable stratification of patients according to the risk of NIV failure. The model is to be used in order to determine adequate level of care and monitoring, that is, a setting within a hospital, for provision of efficent and safe ventilatory support for all patients. Methods: This 39-month prospective observational study was performed at the Institute for Pulmonary Diseases of Vojvodina in Sremska Kamenica, which included 250 consecutive patients hospitalized due to severe exacerbation of COPD with respiratory acidosis. NIV was applied as pressure support mode of ventilation with the ventilators brand Covidien, type Airox Supportair, with oro-nasal mask. Initial parameters were: expiratory positive airway pressure &ndash; EPAPof 5 cm H2O and inspiratory positive airway pressure - IPAP of 12 cm H20, which were further adjusted towards the IPAP of 15-20 cmH2O, or according to the clinical response. The following data were recorded for each patient: sex, age, earlier longterm oxygen therapy, NIV episode during the previous hospitalizations, co-morbidities through Charlson index, time elapsed from admission to NIV initiation, initial blood gas values: pH, bicarbonates, PaCO2 and PaO2, initial SpO2 and PaO2/FiO2, the subsequent changes inthe blood gas values after one hour: pH, PaCO2 and PaO2, initial vital signs - heart rate, respiratory rate, consciousness level by Glasgow coma scale (GCS), body temperature, sistolic blood pressure, urine output, and then modified early warning score - MEWS, presence of consolidation on chest X-ray, tolerance, setting where NIV was applied. Primary outcome was NIV failure defined as endotracheal intubation or death during hospitalization caused by respiratory failure. All variables were first tested with univariate analysis, and those with statistical significance were further subjected to multivariate logistic regression, in order to generate an adequate statistical model. Results: Amongst the total of 250 patients, NIV was successfully applied in 164 patients (65.6 %). There were 139 (59.3%) male patients, and average age was 67. According to the univariate analysis, patients with NIV failure had: higher Charlson index (p=0.002, OR 1.293, 95%CI 1.103-1.516), consolidation in &ge;2 quadrants (p=0.000, OR 5.384, 95%CI 2.487-11.655), longer time from admission to NIV initiation (p=0.0034, OR 1.005, 95%CI 1.000-1.009), increased heart rate (p=0.031, OR 2.292, 95%CI 1.080-4.864), GCS &le;11 (p=0.042, OR 1.000, 95%CI 0.165-0.969), higher MEWS score (p=0.000, OR 1.708, 95%CI 1.410-2.068), lower initial pH (p=0.004, OR 0.002, 95%CI 0.000-0.147), poorer tolerance (p=0.000, OR 2.102, 95%CI 0.145-0.339). The setting were NIV was applied influenced the outcome &ndash; odds for NIV failure were twice as high for the patients on general wards (p=0.006, OR 2.102, 95%CI 1.236-3.574). After the multivariate logistic regression, the following variables were identified as independent predictors of outcome: Charlson index (p=0.043, OR 1.246, 95%CI 1.007- 1.541), MEWS score (p=0.010, OR 1.394, 95%CI 1.083-1.795), initial pH (p=0.030, OR 0.642, 95%CI 0.430-0.958) and tolerance (p=0.000, OR 0.230, 95%CI 0.141-0.376). Conclusions: Patients with higher Charlson index (&gt; 6 points) and MEWS score (&gt;4 points), lower initial pH (&lt;7.29) and tolerance (&lt;4) are at a higher risk for nonivasive ventilation failure. High-risk patients should be admitted and ventilated at high dependency or intensive care units, while the low-risk patients may receive non-invasive ventilatory support on general wards, with adequate monitoring and under the trained staff supervision.</p>

<p>UVOD: Početak multiple skleroze (MS) u dečijem uzrastu je dijagnostički i terapijski izazov. I ako rani početak MS-a uglavnom ukazuje na dobru kratkoročnu prognozu, neka deca razviju te&scaron;ku onesposobljenost, fizičku ili kognitivnu, a vi&scaron;e od 50% obolelih uđe u sekundarno progresivnu formu bolesti pre 30. godine života. Rana dijagnoza je neophodna za uvođenje imunomodulatorne terapije, kojom se obezbeđuje dobra dugoročna prognoza. CILJ: Analiza parametara koji bi omogućili ranu dijagnozu multiple skleroza sa ranim početkom u odnosu na simptome, sprovedene dijagnostičke procedure i tok bolesti. Sagledavanje inicijalnih kliničkih manifestacija multiple skleroze, prisustva ologoklonaliteta, nalaza MRI endokranijuma i njihovih osobenosti u dečijoj populaciji uz komparaciju sa inicijalnim kliničkim manifestacijama kod pacijenata obolelih od multiple skleroze u odraslom dobu. MATERIJALI METODE: Ova retrospektivno/ prospektivna studija obuhvata pacijente lečene na Klinici za neurologiju KCV u Novom Sadu u periodu od dvanaest godina, od januara 2003. godine do januara 2015. godine sa znacima i simptomima inicijalne demijelinacione bolesti CNS. Od ove kohorte izdvojeno je dve grupe pacijenata; prva grupa pacijenata kod kojih je bolest nastala pre 18. godine života, i druga grupa uzrasta od 20-55 godina. Pacijenti su epidemiolo&scaron;ki obrađeni prema godinama početka bolesti, polu, porodičnoj istoriji, simptomima na početku bolesti (inicijalni simptom), toku bolesti- pojavi drugog relapsa i vremena do pojave drugog relapsa, nalazu MRI, nalazu evociranih potencijala i prisustvo oligoklonalnih traka u likvoru. Tokom praćenja beleži se vreme do drugog relapsa i tip relapsa. Tražila se korelacija između kliničkih i dijagnostičkih rezultata sa brzinom pojave drugog relapsa. Za testiranje razlika između grupa kori&scaron;ćen je Pirsonov hi-kvadrat test, a za testiranje jačine povezanosti kori&scaron;ćeno je Kramerovo V. Neparametrijski podaci su obrađivani Men-Vitni U testom. REZULTATI: Od ukupnog broja ispitanika, u grupi pacijenata sa ranim početkom MS-a odnos ženskog i mu&scaron;kog pola je bio 1,3:1, a u grupi pacijenata sa uobičajenim početkom MS-a 2,2:1. Iz dobijenih rezultata vidimo da ima manje nego &scaron;to je očekivano pacijenata rođenih u mesecima decembru 4,6% i januaru (5,9%), a vi&scaron;e nego &scaron;to je očekivanu u mesecima martu (11,3%) i julu (10,6%), &scaron;to nije statistički značajno (p=0,726). Prema manifestaciji bolesti kod dece 17,6% ima polisimptomatski početak, a kod odraslih 37,6% ima polisimptomatski početak.Polisimptomatski početak statistički je značajno vi&scaron;e zastupljen kod odraslih pacijenata (p=0,020).Poremećaj piramidnog sistema (P=0,010) i senzorne smetnje (P=0,006) su zastupljeniji kao inicijalni stimptom u grupi odraslih.Nisu nađene statistički značajne razlike u zastupljenosti optičkog neuritisa (p=0,366 ili p&gt;0,05) i ataksije /stablarne simptomatologije (p= 0,791) u ove dve grupe. Najče&scaron;ći inicijalni simptom kod dece, gotovo u istoj razmeri su optički neuritis (35,3%) i ataksija (35,3%). U grupi odraslih pacijenata senzorne smetnje (41,6%) su najče&scaron;ći inicijalni simptom, odmah za njim sledi piramidna simptomatologija (37,6%). Prema nalazu broja lezija na MRI pregledu, u grupi ispitanika sa ranim početkom MS-a vi&scaron;e su zastupljeni oni sa manje od 4 lezije, nego &scaron;to je to slučaj u grupi odraslih. Odnos broja pacijenata sa 4-10 i preko 10 lezija simetričan je u obe grupe. Korelacija između doba početka MS-a i broja lezija viđenih na MRI je statistički značajna i neznatna (P=0,06). Nije nađena statistička značajnost u prisustvu lezija u korpusu kalozumu između ove dve grupe pacijenata ( P=0,920). Primenom Fi&scaron;erovog dvostranog egzaktnog testa koji je u ovom slučaju statistički značajan (p=0,034), možemo reći da se grupa sa ranim početkom MS-a i ona sa uobičajenim početkom statistički značajno razlikuju, tumefaktivne lezije su prisutnije kod ispitanika sa ranim početkom MS-a. Pozitivni oligoklonali su zastupljeniji u grupi odraslih pacijenata ( P= 0,018). U na&scaron;oj grupi ispitanika kada smo pratili vreme pojave drugog pogor&scaron;anja, najkraće godinu dana, u grupi dece 11 pacijenata (21,6%) nije imalo pogor&scaron;anje , dok je 40 pacijenata imalo pogor&scaron;anje (78,4%),. Medijana kod grupe dece za pojavu drugog &scaron;uba bolesti je 12 meseci. U grupi odraslih 22 pacijenta ( 21,8%) nije imalo drugi relaps tokom perioda praćenja, dok je njih 79 (78,2%) imalo drugi relaps. Prosečno vreme u grupi odraslih pacijenata do drugog relapsa je 9 meseci. U grupi dece ne postoje značajne razlike u odnosu broja lezija viđenih na inicijalnom MRI pregledu i vremenu pojave drugog relapsa ( p=0,884) Kod odraslih postoji značajna razlika u vremenu relapsa između grupe sa manje od 4 lezije i grupe sa 4-10 lezija (p=0,09).Korelirali smo pacijente sa pozitivnim i negativnim ologoklonalnim trakama u likvoru u obe grupe sa vremenom nastanka prvog pogor&scaron;anja, pri toj korelaciji nije dobijena statistički značajna razlika ni u grupi dece ( P= 0,598) ni u grupi odraslih (P=0,133). Kod ispitanika sa ranim početkom če&scaron;ća je pozitivna porodična anamneza, u vidu prisustva MS i drugih imunolo&scaron;kih bolesti( P =0,042). ZAKLJUČAK: Polisimptomatski početak je če&scaron;ći kod odraslih, pozitivne oliogoklonalne trake su ređe pozitivne kod dece, kod dece je najče&scaron;ći inicijalni simptom optički neuritis a kod odraslih senzitivne i motorne smetnje. Manje od 4 lezije se če&scaron;će javljaju kod dece na inicijalnom MRI pregledu, &scaron;to je najverovatnije povezano sa vremenom stvarnog početka bolesti i njenom kliničkom manifestacijom. Kod pacijenta sa ranim početkom MS-a duži je period do drugog pogor&scaron;anja. U grupi dece ne postoje statistički značajne razlike u odnosu broja lezija viđenih na inicijalnom MRI pregledu i vremenu pojave drugog relapsa. Kod odraslih postoji značajna razlika u vremenu relapsa između grupe sa manje od 4 lezije i grupe sa 4-10 lezija. Inicijalne manifestacije MS-a u dečijem uzrastu ne razlikuje se u mnogome od MS-a kod odraslih po karakteristikama i toku bolesti.</p> / <p>INTRODUCTION: Тhe onset of multiple sclerosis (MS) in childhood poses diagnostic and therapeutic challenges. Althougth the onset of MS in childhood typically predicts a fevoruable short/term prognosis, some children are severy disabled. Etiher physically or cognitively, and more then 50% are predicted to enter the secondary-progressive phase of the disease by the age of 30 years. Immunomodulatory therapies for MS and their safe application in children can improve long-therm prognosis. AIM: We saught to identifay clinical and diagnostic features in children wich inplicate to early diagnosis of MS in children. We aimd to determine the clinical features, cerebro spinal fluid, magnetic resonance imagin (MRI) features of children and their comparation with adult MS patients. METHODS: In this retrospective/prospective study we present data from 152 patients with clinical isolated syndrom (CIS) for the first time, which are obtained throught Clinic of Neurology , Clinical Centre of Vojvodina, Novi Sad from January 2003 to January 2015g. Patients were divided into two grups - in first group patients 51 with early onset of disease before 18 years, and second group patients with adult onset desease (20-55 year). Patients wer observed for a minimum one year. The common presenting symptoms, gender, MRI finding, oligoclonal band (OCB) and Visual evoked potential findings, corse of disease, family history were compared between the two groups and with thime of second relaps. To test the difference between groups was used Chi-square Pearson product moment test, and to test the strength of connection used is a Kramer V. Population data are processed Men-Whitney U test. RESULTS: Of the total number of respondents, in the Group of patients with early beginning MS the ratio of women and men was 1.3:1, and in the group of adult MS patients 2, 2:1. From the results we can see that fewer than expected has patients born in the months December ( 4.6%) and January (5.9%), and higher than expected in a March (11.3%) and July (10.6%), which is not statistically significant (p = 0,726). According to the manifestation of disease in children 17.6% has a polifocal onset, and in adults 37.6% has a polifocal onset. Polifocal beginning is significantly over represented in adult MS patients (p = 0,020). Motor disorder (P = 0,010) and sensory disabilities (P = 0.006) are more present as the initial manifestation illness in the adult. They not found statistically significant differences in the representation of optic neuritis (p = 0,366 or p &gt; 0.05) and ataxia (p = 0.791) in these two groups. The most common initial symptom in children, almost in the same scale are the optical neuritis (35.3%) and ataxia 6 (35.3%). In a group of adult patients sensory disturbances (41.6%) are the most common initial symptom, right behind him follows a motor disturbens (37.6%). According to the number of lesions on the MRI exam, in a group of subjects with early MS more are they less than four lesions, than is the case in the group adults. The ratio of the number of patients with 4-10 and over 10 symmetrical lesions in both groups. Correlation between the time of the beginning of the MS and the number of lesions seen on MRI is statistically significant and insignificant (P = 0.06). There was no statistical significance in the presence of lesions in the corpus callosum indicates between these two groups of patients (P = 0,920). Application of Fisher the exact test case that is in this case a statistically significant (p = 0.034). We can say that the group with the early start of MS and the one with the usual beginning of significantly different, tumefactiv lesions are present in patients with early onset MS, Positive oligoclonal bands are more present in a group with adult MS patients (P = 0.018). In our group of respondents when we track time appear another relapse, minimum one year, 11 children (21,6%) had no deterioration, while the 40 children had worsening (78,4%). The median at groups of children for the appearance of second relapse is 12 months. In the adult these 22 (21,8%) had another relapse for tracking period, while 79 (78.2%) had another relapse. The average amount of time in the adult patients relapse to another is 9 months. In a group of children there are no statistically significant differences in the relative number of lesions seen on the initial MRI examination and time show up another relapse (p = 0,884). In adults there is a significant difference in relapse time between groups with fewer than four lesions and groups with 4-10 lesions (p = 0.09). Pressures are patients with positive and negative ologoclonal bands in the cerebrospinal fluid in both groups with the time of occurrence of the first downturn, when the correlation is not get statistically significant difference in the children (P = 0.598) or in a group of adults (P = 0,133). In patients with early starting stacks is a negative family history, and often the presence of MS and other immunological diseases (P = 0,042). CONCULSIONS: Polisifocal beginning is more common in adults, positive oliogoklonalne bands are less positive in children, with children being the most common initial symptom is optic neuritis, in adult sensitive and motor disturbances. Tumefactiv lesions are present in patients with early onset MS. Less than four lesions are more common in children on the initial MRI examination, which is probably connected with the time of the real onset of the disease and its clinical manifestation n the group of children there are no statistically significant differences in relation to the number of lesions seen on MRI at the initial examination and the timing of another relapse. For adults there is a significant difference in time of relapse between the groups with less than 4 lesions and groups with 4-10 lesions. Children onset MS does not significantly differ from that it has been typically seen in adults in terms of major clinical manifestations and course of disease.</p>

A hepatite C é um processo inflamatório do tecido hepático que acomete milhões de pessoas em todo mundo. A evolução crônica da doença pode levar a transformação da fibrose hepática em cirrose e carcinoma hepatocelular em um grande número de casos. A avaliação dos graus de fibrose hepática é importante para o estudo da gravidade e progressão da doença, bem como decisão terapêutica e avaliação de sua eficácia. Os métodos não invasivos de avaliação da fibrose hepática têm sido uma opção aos possíveis riscos da biópsia hepática, ainda considerada o melhor método de avaliação de fibrose hepática. No presente trabalho, 107 pacientes portadores de hepatite C foram submetidos à biópsia hepática e Elastografia transitória hepática, 106 pacientes APRI e FIB4, ELF em 68 pacientes e ARFI em 51 pacientes. Usando a área abaixo da Curva ROC, AUROC, para obter a acurácia da fibrose hepática, encontramos na fibrose significativa ( >= F2): Elastografia transitória hepática: 0,83; FIB4: 0,76; ELF: 0,70; APRI: 0,69; ARFI: 0,67; na fibrose avançada ( >= F3): Elastografia transitória hepática: 0,85; ELF: 0,82; FIB4: 0,77; ARFI: 0,74; APRI: 0,71 e na cirrose ( >= F4) APRI: 1; FIB4: 1; Elastografia transitória hepática: 0,99; ARFI: 0,96; ELF: 0,94. Podemos dizer que em todos os graus de fibrose avaliados, a Elastografia transitória hepática foi o método que apresentou a melhor acurácia. Em se de tratando de cirrose (>=F4), todos os métodos não invasivos apresentam excelente acurácia. Utilizando o método Obuchowski, encontramos em cada grau de fibrose hepática classificado pelo escore METAVIR as acurácias: F1= Elastografia transitória hepática: 0,81; ARFI: 0,78; APRI: 0,72; FIB4: 0,67; ELF: 0,44; F2= Elastografia transitória hepática: 0,73; FIB4: 0,68; ELF: 0,63; APRI: 0,60; ARFI: 0,53; F3= ELF: 0,77; Elastografia transitória hepática: 0,70; FIB4: 0,67; ARFI: 0,64; APRI: 0,60 e F4: APRI e FIB4: 1; Elastografia transitória hepática: 0,98; ARFI: 0,96; ELF: 0,82. A Elastografia transitória hepática se mantém como um método eficiente para todos os graus de fibrose, sendo que nos extremos apresenta discreta superioridade em relação aos graus intermediários. A acurácia de todos os métodos é superior em F4 / Hepatitis C is an inflammatory condition of the hepatic tissue that affects millions worldwide. The chronic stages of the disease turns from hepatic fibrosis into cirrhosis and hepatocellular carcinoma in many cases. The evaluation of fibrosis staging is important for prognosis, as well as understanding the progression of the disease, choice of treatment options and assessing their effectiveness. Non-invasive methods of fibrosis assessment have increasingly become alternatives to liver biopsy, which is still considered the best method of fibrosis assessment. In this study, 107 consecutive patients with hepatitis C virus were submitted to liver biopsy and transient elastography, 106 underwent APRI and FIB-4, 68 underwent ELF and 51 underwent ARFI. Using the area under ROC curve (AUROC) to obtain the degree of accuracy of each test, the following cutoffs were found for significant fibrosis (F >= 2): transient elastography: 0,83; FIB4: 0,76; ELF: 0,70; APRI: 0,69; ARFI: 0,67; For advanced fibrosis (F>=3): transient elastography: 0,85; ELF: 0,82; FIB4: 0,77; ARFI: 0,74; APRI: 0,71; For cirrhosis (F >= 4): APRI: 1; FIB4: 1; transient elastography: 0,99; ARFI: 0,96; ELF: 0,94. Of the methods assessed, transient elastography presented the greatest diagnostic accuracy across all levels of fibrosis. When assessing cirrhosis (F>= 4), all of these non-invasive methods showed excellent diagnostic accuracy. Using the Obuchowski method, the accuracy of each degree of fibrosis categorised by the METAVIR score was determined: F1= transient elastography: 0,81; ARFI: 0,78; APRI: 0,72; FIB4: 0,67; ELF: 0,44; F2=transient elastography: 0,73; FIB4: 0,68; ELF: 0,63; APRI: 0,60; ARFI: 0,53; F3= ELF: 0,77; transient elastography: 0,70; FIB4: 0,67; ARFI: 0,64; APRI: 0,60; F4: APRI and FIB4: 1; transient elastography: 0,98; ARFI: 0,96; ELF: 0,82. Transient elastography remained the most effective method for all degrees of fibrosis, although at the higher levels this superiority was less than at the intermediate levels. The accuracy of all methodologies was best at F >= 4

Objetivos: Analisar o potencial da oftalmoscopia confocal de varredura a laser, através do Heidelberg Retina Tomograph (HRT), para predizer o risco de progressão em pacientes com suspeita de glaucoma. Comparar os resultados obtidos com o índice de probabilidade de glaucoma (GPS) do HRT aos resultados da análise de regressão de Moorfields (ARM), dos parâmetros morfométricos e da avaliação das fotografias estereoscópicas. Métodos: Uma coorte foi selecionada com 223 pacientes com suspeita de glaucoma, que foram seguidos por um período médio de 64,9 ± 37,3 meses. A suspeita de glaucoma baseou-se na aparência do disco óptico e/ou na pressão intraocular elevada (> 21 mmHg). Todos os participantes apresentavam dois exames de campo visual normais ao entrar no estudo. Conceituou-se progressão como o desenvolvimento de um defeito confirmado de campo visual ou deterioração do disco óptico na avaliação seriada das estereofotografias. A associação entre os resultados do HRT na época do início do acompanhamento e a progressão para glaucoma foi investigada através de modelos de regressão do tipo Cox. Usou-se o C-index para a comparação entre os modelos com os diversos parâmetros do HRT, isolados ou ajustados para os outros já conhecidos fatores de risco para progressão (idade, espessura corneana, pressão intraocular e pattern standard deviation PSD). Resultados: No período do estudo, 46 pacientes (21%) apresentaram progressão. Na análise multivariada, o GPS, a ARM e diversos parâmetros morfométricos foram preditivos para progressão, assim como a avaliação subjetiva das estereofotografias. Cada GPS 0,1 maior foi associado com um aumento de 23% no risco de progressão (C-index de 0,69). Os resultados anormais nas classificações finais do GPS e da ARM foram associados a aumentos de 3 e 2 vezes no risco de progressão, respectivamente (C-indexes de 0,70 e 0,68, respectivamente). O parâmetro com o melhor C-index foi a área seccional tranversa da camada de fibras nervosas (0,72). Uma área 0,3 mm2 menor foi associada a um risco 62% maior de progressão. A comparação do valor preditivo entre os modelos com o GPS e com a avaliação subjetiva das estereofotografias foi similar (C-indexes de 0,69 e 0,68, respectivamente). Conclusão: Nesse estudo observamos que as análises objetivas do disco óptico e da região peripapilar obtidas com o HRT contribuíram na avaliação do risco de progressão em pacientes com suspeita de glaucoma. O GPS mostrou-se tão eficaz quanto os parâmetros morfométricos e a análise de regressão de Moorfields, e a comparação do desempenho dos modelos contendo a avaliação subjetiva das estereofotografias e aqueles contendo a avaliação objetiva pelo GPS não mostrou diferenças significativas / Purpose: To evaluate the ability of baseline confocal scanning laser ophthalmoscopy, using the Heidelberg Retina Tomograph (HRT), in predicting the development of progression in patients suspected of having glaucoma. In addition, the study also aimed to compare the predictive abilities of the glaucoma probability score (GPS) with those of the Moorfields regression analysis (MRA) and stereometric parameters, and to compare the performance of the HRT with that of subjective evaluation of optic disc stereophotographs. Methods: This longitudinal study included a cohort of 223 eyes suspected of having glaucoma, which were followed for an average of 64.9 ± 37.3 months. Included suspects had a suspicious appearance of the optic disc and/or elevated intraocular pressure, but normal visual fields. Progression was defined as the development of either repeatable abnormal visual fields or glaucomatous structural deterioration in the appearance of the optic disc during the study period. The association between baseline HRT parameters and progression was investigated by Cox regression models. The comparison between models with HRT parameters, individually or combined with other known risk factors (age, central corneal thickness, pattern standard deviation and intraocular pressure), performed by comparing their C-indexes. Results: Forty-six (21%) eyes converted during the study period. In multivariable models, the GPS, the MRA, and the stereometric parameters were all predictive of progression. A GPS 0.1 larger was associated with an increase of 23% in the risk of progression (C-index of 0.69). Abnormal final classifications for the GPS or the MRA were associated with a three-fold and two-fold increase in the risk of progression, respectively (with C-indexes of 0.70 and 0.68, respectively). The parameter with the best C-index was the nerve fiber layer cross-sectional area (0.72). An area 0.3 mm2 smaller was associated with a 62% higher risk of an individual progress. The comparison between models with the HRT parameters and those with the subjective stereophotograph evaluation had similar results (C-indexes of 0.69 and 0.68, respectively). Conclusion: In this study, we were able to show that the objective structural assessment of the optic disc and peripapillary area obtained with the HRT was significantly predictive for progression in suspected individuals. The GPS was as predictive as the other HRT parameters, and no significant differences were observed between models with the GPS and those with the subjective assessment of the stereophotographs.

INTRODUÇÃO: A persistência de um microambiente cronicamente inflamado no estômago tem sido descrita como um componente crítico tanto para a iniciação, quanto para a progressão tumoral. Além disso, variações genéticas tem demonstrado influenciar na variabilidade interindividual da resposta inflamatória. Desta forma, esse estudo teve como objetivo investigar a associação de polimorfismos em genes relacionados à resposta inflamatória com o risco para o desenvolvimento do câncer gástrico, com suas variáveis anatomopatológicas e com a sobrevida global e livre de doença em uma amostra da população Brasileira. MÉTODOS: Dezesseis variantes genéticas selecionadas em onze genes (COX-2, OGG1, TNFB, TNFA, HSPA1L, HSPA1B, VEGFA, IL17F, LGALS3, PHB e TP53) foram genotipadas em 262 indivíduos controles e 178 pacientes diagnosticados com câncer gástrico. As análises de associações genéticas foram realizadas em diferentes modelos (Genótipos, Alelos, Dominante e Recessivo) considerando a amostra total de casos (N=178) e estratificada somente para os casos com o subtipo histológico difuso de Lauren (N=112). Também foi investigado o desequilíbrio de ligação entre os polimorfismos e as análises de associação com os haplótipos formados foram realizadas por meio dos softwares Haploview e PLINK. RESULTADOS: No estudo caso-controle, indivíduos portadores do alelo Pro do polimorfismo rs1042522 (TP53) apresentaram risco cerca de duas vezes maior em desenvolver o câncer gástrico em análise multivariada, sendo esse risco ainda maior quando considerado somente os casos com o subtipo difuso. Por outro lado, a presença do alelo A do polimorfismo rs699947 (VEGFA) foi associada com uma proteção para o câncer gástrico. Em relação às variáveis anatomopatológicas, os polimorfismos rs689466 (COX-2); rs1052133 (OGG1); rs699947, rs833061 e rs2010963 (VEGFA); rs4644 (LGALS3) e rs1042522 (TP53) foram significativamente associados com características de pior progressão da doença, enquanto que rs5275 (COX-2); rs2227956 (HSPA1L) e rs3025039 (VEGFA) foram associados às variáveis de melhor progressão da doença, na amostra total de casos. Também foi observado que o polimorfismo rs909253 (TNFB) foi capaz de predizer uma melhor progressão da doença quando considerado somente os casos com subtipo difuso. Além disso, em relação ao impacto sobre a sobrevida, rs909253 (TNFB) foi associado a um melhor prognóstico quando analisadas ambas as curvas de sobrevida global e livre de doença, enquanto que portadores do alelo His do polimorfismo rs4644 (LGALS3) apresentaram um pior prognóstico com menor tempo de sobrevida livre de doença. Por fim, nas análises de associação com os haplótipos, identificamos que o haplótipo CTC (formado por rs699947, rs833061 e rs2010963 do gene VEGFA), demonstrou ser um fator de maior suscetibilidade ao câncer gástrico. Também foram observadas associações entre o haplótipo GG (TNFB/TNFA) e invasão perineural; haplótipo ACG (VEGFA) e invasão sanguínea; haplótipo CTC (VEGFA) e invasão para outros órgãos; haplótipo GT (rs689466 e rs5275 do gene COX-2) e subtipo histológico intestinal. CONCLUSÕES: Os resultados desse estudo nos ajudaram a esclarecer o potencial papel desses polimorfismos em genes envolvidos com a modulação da resposta inflamatória na patogênese do câncer gástrico, indicando que variantes genéticas do hospedeiro atuam conjuntamente com outros fatores, influenciando na suscetibilidade, progressão e prognóstico dessa doença / INTRODUCTION: The chronic inflammatory microenvironment in the stomach has been described as a critical component for both tumor initiation and progression. Furthermore, genetic variants have shown to influence the interindividual variations in the inflammatory response. Therefore, we aimed to investigate whether polymorphisms in inflammatory response related-genes were associated with risk for gastric tumor development, clinical outcomes, overall and disease free survival of this disease in a Brazilian population sample. METHODS: Sixteen selected genetic variants in eleven genes (COX-2, OGG1, TNFB, TNFA, HSPA1L, HSPA1B, VEGFA, IL17F, LGALS3, PHB and TP53) were genotyped in 262 control individuals and 178 gastric cancer patients. Genetic association analyses were investigated in different models (Genotype, Allele, Dominant and Recessive) in both total sample (N=178) and stratified for the diffuse histological subtype based on Lauren´s classification (N=112). We also calculated the linkage disequilibrium among the polymorphisms and the haplotype associations were carried out using Haploview and PLINK softwares. RESULTS: In the case-control study, rs1042522 (TP53) Pro allele carriers presented about 2-fold higher risk for developing gastric cancer in a multivariate analysis and this association was even stronger when analyzing only cases with the diffuse subtype. On the other hand, the presence of A allele of rs699947 (VEGFA) was associated with a protection for developing gastric cancer. About the significant associations detected with the clinicopathological features, we found that rs689466 (COX-2); rs1052133 (OGG1); rs699947, rs833061 and rs2010963 (VEGFA); rs4644 (LGALS3) and rs1042522 (TP53) were able to predict outcomes associated with a worse progression of the disease while rs5275 (COX-2); rs2227956 (HSPA1L) and rs3025039 (VEGFA) were associated with better outcomes in the total sample. We also observed that the polymorphism rs909253 (TNFB) was able to predict a better outcome only for the individuals diagnosed with the diffuse subtype. Additionally, regarding the impact on the survival curves, rs909253 (TNFB) was associated with a better prognosis when analyzing both the overall and disease-free survivals while rs4644 (LGALS3) His allele carriers presented a worse prognosis with shorter disease-free survival. Finally, concerning the haplotype associations, we found that CTC haplotype (composed by rs699947, rs833061 and rs2010963 of VEGFA) showed an association with gastric malignancy. We also observed associations between GG haplotype (TNFB/TNFA) and perineural invasion; ACG haplotype (VEGFA) and venous vascular invasion; CTC haplotype (VEGFA) and invasion to other organs and GT haplotype (rs689466 and rs5275 of COX-2 gene) and the intestinal histologic subtype. CONCLUSIONS: These results helped us to clarify the potential role of these polymorphisms in genes involved in the modulation of the inflammatory response in the pathogenesis of gastric malignancy, highlighting that the host genetic variants act together with other factors to influence in the susceptibility, progression and prognosis of gastric cancer

<p>Hronična opstruktivna bolest pluća je jedna od najče&scaron;ćih hroničnih bolesti pluća i važan uzrok morbiditeta i mortaliteta u svetu. Egzacerbacije predstavljaju značajan događaj u toku bolesti, jer imaju negativan uticaj na mortalitet, kvalitet života, opadanje plućne funkcije i povećanje tro&scaron;kova lečenja. Cilj rada je utvrditi nezavisne faktore rizika za egzacerbaciju i smrtni ishod tokom jednogodi&scaron;njeg praćenja obolelih od hronične opstruktivne bolesti pluća i kreiranje prediktivnog modela za neželjeni događaj. U ispitivanje je uključeno 200 pacijenata sa potvrđenom dijagnozom hronične opstruktivne bolesti pluća, koji su lečeni prema preporukama smernice Globalne inicijative za hroničnu opstruktivnu bolest pluća. Pacijenti su praćeni godinu dana, evaluirani na kontrolnim pregledima i beležen je broj egzacerbacija na osnovu vanrednih poseta i eventualni smrtni ishod. Statističkom obradom podataka utvrđeni su nezavisni prediktori egzacerbacije (starost &gt; 65 godina, test procene hronične opstruktivne bolesti pluća &gt; 9, modifikovana skala dispneje &gt; 2, saturacija hemoglobina kiseonikom &le; 93%) i smrtnog ishoda (starost &gt;65 godina, potreba za primenom antiagregacione terapije, brzina maksimalnog ekspiratornog protoka na 25% vitalnog kapaciteta &le; 1,16 l, modifikovana skala dispneje &gt;2, puls &gt; 89). Od navedenih nezavisnih faktora su kreirani modeli za predikciju neželjenih događaja. Unutra&scaron;njom validacijom modela dokazana je dobra prediktivna vrednost oba matematička modela, bez statistički značajne razlike opserviranog i očekivanog procenta pojave egzacerbacije i smrtnog ishoda tokom praćenja pacijenata obolelih od HOBP.</p> / <p>Chronic obstructive pulmonary disease is one of the most common chronic lung diseases and is an important cause of morbidity and mortality in the world. Exacerbations are an important event in the course of the disease, as they have a negative impact on mortality, quality of life, lung function decline and increased costs of treatment. The aim of study is to identify risk factors for exacerbation or death during the one-year follow-up of patients with chronic obstructive pulmonary disease, and creation of predictive models for exacerbation and mortality during the follow-up period. The study included 200 patients with a confirmed diagnosis of chronic obstructive pulmonary disease who have had the therapy according to the Global initiative for chronic obstructive airway diseases guidelines. Patients were followed for one year, evaluated the number of exacerbations on the basis of emergency visits and eventual death. With statistical data processing there were identified independent predictors of exacerbations (age &gt; 65 years, COPD Assessment Test &gt; 9, modified Medical Research Council scale &gt;2, oxygen saturation &le; 93%) and death (age &gt; 65 years, the need for application of antiplatelet therapy, the rate of maximum expiratory flow at 25% of vital capacity &le; 1,16 l, modified Medical Research Council scale &gt;2, heart rate &gt; 89th). Of these independent factors was created a models for the prediction of adverse events during the one-year mark of COPD patients. Internal validation showed good predictive value of both models. No difference between the observed and the expected percentage of occurrence of exacerbations or death during the the follow-up period.</p>

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Normal";mso-tstyle-rowband-size:0;mso-tstyle-colband-size:0;mso-style-noshow:yes;mso-style-priority:99;mso-style-qformat:yes;mso-style-parent:"";mso-padding-alt:0in 5.4pt 0in 5.4pt;mso-para-margin-top:0in;mso-para-margin-right:0in;mso-para-margin-bottom:10.0pt;mso-para-margin-left:0in;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri","sans-serif";mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}</style><![endif]-->Uvod: Traumatsko moždano o&scaron;tećenje (TMO) predstavlja globalni zdravstveni problem koji pogađa oko 10 miliona ljudi godi&scaron;nje &scaron;irom sveta. Te&scaron;ka traumatska moždana o&scaron;tećenja (TTMO) čine 10% svih TMO i imaju visoku stopu mortaliteta i neizvestan oporavak. Ranije prepoznavanje sistemskih faktora koji utiču na ishod lečenja može da ima značajan uticaj na pravovremeno započinjanje terapijskih mera i smanjivanje morbiditeta i mortaliteta. Cilj istraživanja: Identifikovati sistemske faktore koji imaju značajan uticaj na ishod lečenja povređenih sa TTMO u Jedinici intenzivnog lečenja (JIL) tokom prvog dana hospitalizacije. Metodologija: Ispitivanje je sprovedeno kao retrospektivno-prospektivna studija koja je obuhvatila 115 povređenih ispitanika sa TTMO koji su hospitalizovani u JIL Urgentnog centra Kliničkog centra Vojvodine (UC KCV) u periodu od 1.01.2014.-1.10.2017. Iz medicinske dokumentacije, za svakog ispitanika uključenog u istraživanje su uzeti u razmatranje i analizu sledeći parametri u toku prvih 24 časa od momenta prijema u JIL: demografske i op&scaron;te karakteristike ispitanika od značaja za istraživanje i sistemski prediktivni faktori (sistolni i srednji arterijski pritisak- SAP/MAP, glikemija-&Scaron;UK, telesna temperatura-TT, pH, parcijalni pritisak kiseonika-PaO2 i parcijalni pritisak ugljem dioksida- PaCO2) registrovani u pet vremenskih tačaka (0h, 6h, 12h,18h, 24h). Svi gore navedeni podaci su posmatrani i analizirani kao prediktorski faktori tj. nezavisne varijable u odnosu na zavisnu varijablu &bdquo;ishod lečenja&ldquo; definisanu kao Glazgovska skala ishoda (Glasgow outcome scale-GOS) nakon otpusta povređenih iz JIL na Kliniku za neurohirurgiju KCV i GOS nakon otpusta iz Klinike za neurohirurgiju KCV i &bdquo;tok lečenja&ldquo; definisan kroz dužinu boravka povređenih u JIL UC KCV, dužinu boravka na Klinici za neurohirurgiju KCV, odnosno ukupno trajanje hospitalizacije u KCV, kao i otpust kući ili u odgovarajući rehabilitacioni centar. Statistička analiza je izvr&scaron;ena pomoću statističkog paketa IBM SPSS 23. Podaci su predstavljeni tabelarno i grafički, a statistička značajnost određivana je na nivou p &lt; 0,05. Prikupljeni podaci su obrađeni adekvatnim statističkim metodima. Rezultati: Sistemski faktori koji su se izdvojili kao prediktori smrtnog ishoda (GOS 1) kod povređenih sa TTMO tokom prvog dana boravka u JIL su upotreba vazoaktivne potpore i glikemija. Upotreba vazoaktivne potpore povećava verovatnoću za smrtni ishod 4,7 puta (OR=0,214; 95%CI: 0,096-0,479; p&lt;0,05). i vrednosti glikemije &gt; 10 mmol/l povećavaju verovatnoću za smrtni ishod u nultom satu (OR= 0,240, 95%CI: 0,087-0,662; p=0,05) i u 24 satu (OR=0,206, 95%CI: 0,037 &ndash; 0,929; p=0,05). Sa svakim porastom telesne temperature za jednu jedinicu u posmatranom intervalu raste verovatnoća za pozitivan ishod (OR =2,118 , 95%CI: 1,097 &ndash; 4,091; p&lt;0,05) i vrednosti glikemije u intervalu od 4-8 mmol/l povećavaju verovatnoću za pozitivan ishod 2,5 puta. Sistemski faktori koji su se izdvojili u smislu predikcije ishoda lečenja ispitanika nakon otpusta iz JIL su vrednosti glikemije i telesna temperatura. Vrednost glikemije na prijemu u intervalu od 6,9 do 7,4 mmol/l povećavaju verovatnoću boljeg oporavka (GOS 4-5 vs. GOS 2-3). Niže vrednosti glikemiije u narednim vremenskim tačkama (6h, 12h, 18h) takođe povećavaju verovatnoću za bolji oporavak. Ukoliko je telesna temperatura u 6-om i 12-om satu, vi&scaron;a od 36,5 &deg;C veća je verovatnoća za bolji neurolo&scaron;ki oporavak, prilikom otpusta iz JIL, odnosno Klinike za neurohirurgiju KCV. Ispitanici koji su imali vi&scaron;e vrednosti telesne temperature su imali duže trajanje hospitalizacije (OR=4,096; 95%CI; 0,709-7,483;p&lt;0,05). Na dužinu boravka u JIL, kao i na otpust kući ili odgovarajući rehabilitacioni centar nije imao uticaj nijedan posmatrani sistemski faktor. Zaključak: Sistemski prediktivni faktori toka i ishoda lečenja povređenih sa TTMO su upotreba vazoaktivne potpore, glikemija i telesna temperatura.</p> / <p>Introduction: Traumatic brain injury (TBI) is a global health problem that affects about 10 million people worldwide annually. Severe traumatic brain injury (STBI) account for 10% of all TBI and has high morbidity and unreliable recovery. Early recognition of systemic factors that affect the treatment outcome can have a significant impact on the timely initiation of therapeutic measures and the reduction of morbidity and mortality. The objective of the research: to identify systemic factors that have a significant impact on the treatment outcome of the STBI patients in the Intensive Care Unit (ICU) during the first day of hospitalization. Methodology: The study was conducted as a retrospective-prospective study that included 115 injured patients with STBI who were hospitalized in the ICU, Emergency Center (EC) of the Clinical Center of Vojvodina (CCV) in the period from 01.01.2014 to 1.10.2017. From the medical documentation, for each participant involved in the research, the following parameters within the first 24 hours after the admission were considered and analyzed: demographic and general characteristics of the participants of importance for research and systemic predictive factors (systolic and mean arterial pressure-SAP / MAP, glycemia, body temperature -TT, pH, partial pressure of oxygen-PaO2 and partial pressure of carbon dioxide-PaCO2) registered at five time points (0h, 6h, 12h,18h, 24h). All of the above data were observed and analyzed as predictors, ie, independent variables in relation to the dependent variable &quot;treatment outcome&quot; defined as the Glasgow Outcome Scale (GOS) after the transfer from the ICU to the Clinic of neurosurgery of the CCV and GOS after discharge from a Clinic of neurosurgery and &quot;treatment course&quot; defined by length of stay in ICU, or the total duration of hospitalization in CCV, as well as the release to the home or the appropriate rehabilitation center. Statistical analysis was performed using the IBM SPSS 23 statistical package. The data are presented in tables and graphs, and the statistical significance was determined at p &lt;0.05. The collected data were processed with adequate statistical methods. Results: Systemic factors that had predictive value for the lethal outcome (GOS 1) in STBI during the first day of ICU stay were the use of vasopressors and glycemia. The use of vasopressors increases the likelihood of fatal outcome 4.7 times (OR= 0,214; 95%CI: 0,096-0,479; p&lt;0,05) and glycemic values &gt; 10 mmol/l increase the likelihood of fatal outcome on admission (OR=0,240, 95%CI: 0,087-0,662; p=0,05) and after 24 hours (OR=0,206, 95%CI: 0,037 &ndash; 0,929; p=0,05). With each increase in body temperature for one unit in the observed interval, the probability of a positive outcome increases (OR=2,118, 95%CI: 1,097 &ndash; 4,091;p&lt;0,05) and glycemic values in the range 4-8 mmol/l increase the probability of a positive outcome 2.5 times. Systemic factors that predict the treatment outcome of the patients after their discharge from ICU are glycemia and body temperature. The blood sugar on admission in the ICU in the range from 6.9 to 7.4 mmol/l increases the opportunity of a better recovery (GOS 4-5 vs. GOS 2-3). Lower glycemic values at the next time points (6h, 12h, 18h) also increase the opportunity of a better recovery. If the body temperature in the 6th and 12th-hour postadmission is higher than 36.5&deg; C, the greater opportunity for better neurological improvement when the patient is discharged from ICU, or from the Clinic of neurosurgery. Participants who had higher values of body temperature had a longer duration of hospitalization (OR 4.096; 95% CI; 0.709-7.483;p&lt;0,05). The length of the stay in ICU, as well as the release to the home or the appropriate rehabilitation center, was not affected by any observed systemic factor. Conclusion: Systemic predictive flow factors and outcome of treatment factors with STBI use of vasopressors, glycemia and body temperature.</p>

Quantitative pharmacokinetic-pharmacodynamic and disease progression models are the core of the science of pharmacometrics which has been identified as one of the strategies that can make drug development more effective. To adequately develop and utilize these models one needs to carefully consider the nature of the data, choice of appropriate estimation methods, model evaluation strategies, and, most importantly, the intended use of the model. The general aim of this thesis was to investigate how the use of pharmacometric models can improve the design and analysis of clinical trials within drug development. The development of pharmacometric models for clinical assessment scales in stroke and graded severity events, in this thesis, show the benefit of describing data as close to its true nature as possible, as it increases the predictive abilities and allows for mechanistic interpretations of the models. Performance of three estimation methods implemented in the mixed-effects modeling software NONMEM; 1) Laplace, 2) SAEM, and 3) Importance sampling, applied when modeling repeated time-to-event data, was investigated. The two latter methods are to be preferred if less than approximately half of the individuals experience events. In addition, predictive performance of two validation procedures, internal and external validation, was explored, with internal validation being preferred in most cases. Model-based analysis was compared to conventional methods by the use of clinical trial simulations and the power to detect a drug effect was improved with a pharmacometric design and analysis. Throughout this thesis several examples have shown the possibility of significantly reducing sample sizes in clinical trials with a pharmacometric model-based analysis. This approach will reduce time and costs spent in the development of new drug therapies, but foremost reduce the number of healthy volunteers and patients exposed to experimental drugs.

Pharmacodynamic processes and disease progression are increasingly characterized with pharmacometric models. However, modelling options for discrete-type responses remain limited, although these response variables are commonly encountered clinical endpoints. Types of data defined as discrete data are generally ordinal, e.g. symptom severity, count, i.e. event frequency, and time-to-event, i.e. event occurrence. Underlying assumptions accompanying discrete data models need investigation and possibly adaptations in order to expand their use. Moreover, because these models are highly non-linear, estimation with linearization-based maximum likelihood methods may be biased. The aim of this thesis was to explore pharmacometric methods and novel models for discrete data through (i) the investigation of benefits of treating discrete data with different modelling approaches, (ii) evaluations of the performance of several estimation methods for discrete models, and (iii) the development of novel models for the handling of complex discrete data recorded during (pre-)clinical studies. A simulation study indicated that approaches such as a truncated Poisson model and a logit-transformed continuous model were adequate for treating ordinal data ranked on a 0-10 scale. Features that handled serial correlation and underdispersion were developed for the models to subsequently fit real pain scores. The performance of nine estimation methods was studied for dose-response continuous models. Other types of serially correlated count models were studied for the analysis of overdispersed data represented by the number of epilepsy seizures per day. For these types of models, the commonly used Laplace estimation method presented a bias, whereas the adaptive Gaussian quadrature method did not. Count models were also compared to repeated time-to-event models when the exact time of gastroesophageal symptom occurrence was known. Two new model structures handling repeated time-to-categorical events, i.e. events with an ordinal severity aspect, were introduced. Laplace and two expectation-maximisation estimation methods were found to be performing well for frequent repeated time-to-event models. In conclusion, this thesis presents approaches, estimation methods, and diagnostics adapted for treating discrete data. Novel models and diagnostics were developed when lacking and applied to biological observations.

Thesis (Ph.D. in Pharmacology) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 117-147). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;