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Clinical characteristics and immune responses in post-encephalitic syndrome after tick-borne encephalitis
Full text linkIzhodišča. O dejavnikih, ki določajo, kakšna bosta potek in izid klopnega meningoencefalitisa (KME), o (dolgo)trajnih posledicah prebolele bolezni (postencefalitisni sindrom) in o mehanizmih, ki so povezani z neugodnim potekom in izidom bolezni, je malo znanega.
Namen. Namen raziskave je opredeliti klinične značilnosti akutne bolezni, ugotoviti, kateri klinični in/ali laboratorijski parametri so povezani s težjim potekom bolezni in/ali neugodnim izidom, oceniti (dolgo)trajne posledice, ki jih pušča prebolela bolezen, in osvetliti osnovne imunske značilnosti KME.
Metode dela. V raziskavo smo vključili 717 odraslih bolnikov, ki so bili v obdobju od 1. 1. 2007 do 31. 12. 2012 na Kliniki za infekcijske bolezni in vročinska stanja zdravljeni zaradi KME. Pri podskupini 420 bolnikov, ki smo jih povabili na kontrolni pregled leta 2014, 2–7 let po prebolelem KME, smo ocenili dolgoročni izid bolezni. V raziskavo smo vključili tudi kontrolno skupino oseb, ki so se z bolniki ujemale glede na starost in v preteklosti niso prebolele KME. Imunske odzive smo v obdobju akutne bolezni ocenili v serumu in možganski tekočini, 2 meseca in 2–7 let po preboleli bolezni pa le v serumu. Določili smo koncentracije 24 citokinov/kemokinov, ki zastopajo prirojene ter pridobljene Th1-, Th17- ter B-celične odzive.
Rezultati. Multipla regresija je pokazala, da so s težjim potekom KME značilno povezani višja starost bolnikov (razmerje obetov (RO) 1,26, 95 % interval zaupanja (IZ) 1,11–1,44P = 0,001), predhodno cepljenje proti KME (RO 14,23, 95 % IZ 1,72–117,87P = 0,014), nizka koncentracija protiteles IgG proti virusu KME v serumu (RO 0,85, 95 % IZ 0,75–0,96P = 0,009), večja koncentracija levkocitov v krvi (RO 1,45, 95 % IZ 1,13–1,85P = 0,004) ter večja koncentracija C-reaktivnega proteina v serumu (ocenjeni koeficient 1,20, 95 % IZ 0,48–1,91P = 0,001).
Pogostost postencefalitisnega sindroma se zmanjšuje s časom in se stabilizira 12 mesecev po preboleli bolezni, ko ima postencefalitisni sindrom tretjina bolnikovkasneje se zmanjšuje le še njegova teža. Neugoden izid 6 mesecev po preboleli bolezni je povezan s koncentracijo levkocitov v možganski tekočini (RO 1,43, 95 % IZ 1,07–1,93, P = 0,017), po 12 mesecih z izidom bolezni po 6 mesecih (RO 497,89, 95 % IZ 39,42–6289,16, P < 0,001) in 2–7 let po preboleli bolezni z izidom bolezni po 12 mesecih (RO 38,56, 95 % IZ 8,40–177,14, P < 0,001). Bolniki so 2𔂻 let po prebolelem KME navedli večje število nespecifičnih simptomov v primerjavi s kontrolnimi preiskovanci, ki niso preboleli KME, prisotnost vsakega od ponujenih simptomov pa bolj pogosto in bolj stalno. Slabše so ocenili tudi kakovost telesnega in duševnega zdravja, vendar so bile razlike med skupinama majhne in niso bile statistično značilne.
Koncentracije velike večine citokinov/kemokinov v serumu in možganski tekočini se v času akutne bolezni značilno razlikujejo: koncentracije citokinov/kemokinov prirojenega in Th1-pridobljenega imunskega odziva so večje v možganski tekočini, tiste, povezane s pridobljenim Th17- in B-celičnim imunskim odzivom, pa v serumu. Večina predstavnikov prirojenega in pridobljenega Th1-imunskega odziva je povezana s težo akutne bolezni, z neugodnim izidom bolezni pa nismo dokazali statistično značilnih povezav.
Sklep. Raziskava, temelječa na velikem številu dobro definiranih odraslih bolnikov s KME, je omogočila določitev dejavnikov, ki so povezani s težkim potekom in neugodnim izidom KME, ter oceno pogostosti in kliničnih značilnosti postencefalitisnega sindroma. Omogočila je tudi vpogled v imunske značilnosti akutne bolezni ter v vnetne parametre, povezane s težko akutno boleznijo in neugodnim izidom.Background. Information on parameters associated with the severity of tick-borne encephalitis (TBE), on the long-term outcome (post-encephalitic syndrome), and on the mechanisms responsible for the unfavorable clinical course and outcome of TBE are limited.
Aims. The aims of the study were to describe the clinical characteristics of acute TBE, to determine the clinical and/or laboratory parameters associated with the severity of acute illness and/or unfavorable outcome, to assess the frequency and severity of post-encephalitic syndrome at different time points after TBE, and to highlight the basic immune characteristics of TBE.
Methods. Seven hundred seventeen adult patients, diagnosed with TBE and hospitalized at the Department of Infectious Diseases, University Medical Centre Ljubljana, in the period from 1. 1. 2007 to 31. 12. 2012, qualified for the study. In a subgroup of 420 patients who participated in a follow-up visit in 2014, i.e. 2–7 years after TBE, we assessed the long-term outcome of the disease. The study also included control group of subjects of the same age (± 5 years). Immune responses were evaluated in serum and cerebrospinal fluid in the period of acute illness, and in the serum 2 months and 2–7 years after the onset of illness. The concentrations of 24 cytokines /chmokines that represent innate and adaptive Th1, Th17 and B cell responses were determined.
Results. Multivariate regression showed that patient age (odds ratio (OR) 1.26, 95% confidence interval (CI) 1.11–1.44P = 0.001), previous vaccination against TBE (OR 14.23, 95% CI 1.72–117.87P = 0.014), low level of specific TBE virus serum IgG antibodies (OR 0.85, 95% CI 0.75–0.96P = 0.009), blood leukocyte count (OR 1.45, 95% CI 1.13–1.85P = 0.004), and serum C-reactive protein level (estimated coefficient 1.20, 95% CI 0.48–1.91P = 0.001) were associated with severe acute illness.
The frequency of post-encephalitic syndrome diminished over time and stabilized 12 months after the acute illness when it was present in one-third of patientswhereas the severity of post-encephalitis syndrome continued to decline. Unfavourable outcome at 6 months was associated with cerebrospinal fluid leukocyte count (OR 1.43, 95% CI 1.07–1.93, P = 0.017), at 12 months with the disease outcome at 6 months (OR 497.89, 95% CI 39.42–6289.16, P < 0.001), and at the final visit with disease outcome at 12 months (OR 38.56, 95% CI 8.40–177.14, P < 0.001). Unspecific symptoms 2–7 years after TBE were more frequent and more constant in patients than in the control group. Similarly, patients have poorly assessed their physical and mental health, but the differences between the groups were small and were not statistically significant.
The concentrations of most cytokines/chemokines in serum and cerebrospinal fluid were significantly different during the time of acute illness: cytokines and chemokines associated with innate immune responses and Th1 adaptive immune responses were significantly higher in cerebrospinal fluid, whereas mediators associated with Th17 and B cell immune responses were generally higher in serum. The majority of studied cytokines/chemokines of innate and adaptive Th1 immune responses were associated with the severity of acute illness, while statistically significant correlations with the unfavorable outcome of the disease have not been found.
Conclusion. A study based on a large number of well-defined adult patients with TBE enabled the identification of parametrs associated with the severity of acute illness and/or unfavourable (long-term) outcome of TBE, and the assessment of the frequency and severity of postencephalitic syndrome. It also provided an insight into the immune characteristics of acute illness and inflammatory parameters associated with severe acute illness and an unfavorable outcome of TBE
Acute viral respiratory infections among nursing home residents and members of staff
Full text linkS staranjem prebivalstva se veča število oseb s kroničnimi obolenji, upadom mentalnih in motoričnih funkcij ter posledično potrebo po institucionaliziranem varstvu. V Sloveniji prebiva v domovih starejših občanov (DSO) okoli 5% prebivalcev. Zaradi starostnega upada imunskih zmožnosti, pridruženih obolenj in bivalnih posebnosti (bivanja večjega ranljivih števila oseb v skupnih prostorih) predstavljajo okužbe v DSO poseben problem. Okužbe dihal (AOD) so med najpogostejšimi okužbami v DSO, predstavljajo tretjino vseh okužb v DSO, povezane so z največjim številom bolnišničnih obravnav in tudi z najvišjo smrtnostjo. Vodijo lahko v trajni upad fizičnih zmogljivosti starostnikov. Četudi pogostost virusnih AOD s starostjo pada, lahko te potekajo s težjim kliničnim potekom - z znaki akutne okužbe spodnjih dihal (AOSD). Prepoznavanje AOD je lahko pri starostnikih v DSO, zaradi pogosto neznačilne klinične slike, težavno. Poznavanje virusne etiologije in incidence AOD v DSO je pomembno, saj omogoča smiselno na
rtovanje ukrepov za zmanjšanje obolevnosti oskrbovancev.
Bolniki in metode
V 6-mesečno prospektivno raziskavo smo vključili 90 oskrbovancev DSO ter 42 zaposlenih v enem izmed DSO-jev v mariborski regiji. Opazovali smo pojav AOD v obdobju od 5.decembra 2011 do 31. maja 2012 pri oskrbovancih DSO in osebju. AOD smo definirali po McGeer-ovih kriterijih. AOD so dnevno prepoznavale naučene medicinske sestre in potrdila zdravnica ob viziti pri obolelih oskrbovancih. Pridobili smo osnovne podatke, podatke o pridruženih obolenjih ter o cepljenju proti gripi pri vseh sodelujočih v raziskavi. Ob začetku in zaključku raziskave smo vsem sodelujočim odvzeli bris nosnega dela žrela za mikrobiološke preiskave, prav tako tudi ob vsaki epizodi AOD, kjer smo zabeležili tudi klinične simptome in znake obolenja.
V brisu nosnega dela žrela smo s pomočjo molekularne preiskave določili prisotnost genoma virusov gripe A in B, parainfleunce 1-3, rinovirusov, respiratomega sincicijskega virusa, človeškega metapnevmovirusa, koronavirusov, adenovirusov, človeškega bokavirusa in enterovirusov. Prav tako smo v 6 mesečnem obdobju raziskave beležili tedensko število obiskovalcev v sobah sodelujočih oskrbovancev DSO. V statistični analizi smo uporabljali naslednje metode: 6-mesečno incidenčno stopnjo AOD, akutnih okužb zgornjih dihal (AOZD) in AOSD smo podali kot število AOD (oz. AOSD in AOZD) na 1000 oskrbnih dnikategorične spremenljivke smo primerjali s pomočjo hi-kvadrat testa ali Fisherjevega eksaktnega testakorelacijo med spremenljivkama smo preučili s pomočjo korelacijskega koeficienta Kendall τs pomočjo multivariantne Poissonove analize smo preučili vpliv različnih neodvisnih spremenljivk na incidenčno stopnjo AOD pri posameznem oskrbovancu DSO. Povezanost med številom obiskovalcev pri posameznih oskrbovancih in pojavom AOD pri le-teh smo preučevali s pomočjo Poissonove regresije. Kot statistično značilne smo upoštevali rezultate, pri katerih je bil p < 0,05.
Rezultati
V 6-mesečnem opazovalnem obdobju je bila incidenčna stopnja AOD 3,8/1000 oskrbnih dni pri oskrbovancih in 5,9/1000 oskrbnih pri zaposlenih, razlika je statistično pomembna. Starostniki so pogosteje obolevali z AOSD (73%), kot z AOZD (27%), med tem ko so zaposleni obolevali skoraj izključno za AOZD (97%). S pomočjo multivariantne Poissonove analize smo ugotovili, da nobena od vključenih neodvisnih spremenljivk (starost, cepilni status - cepljenje proti gripi, pomičnost in pridružena kronična obolenja (sladkorna bolezen, srčno-žilna, možgansko-žilna obolenja, kronična pljučna obolenja, demenca) ne vpliva na pojav AOD pri oskrbovancih, z izjemo demence. Dementni bolniki so kar 2,5 krat redkeje obolevali z AOD. Prav tako število obiskovalcev ni vplivalo na pojav AOD pri oskrbovancih. Ugotovili smo korelacijo med tedensko incidenčno stopnjo AOD pri zaposlenih in oskrbovancih. Viruse smo dokazali pri 60,7 % epizod AOD pri oskrbovancih DSO in pri 47,7 % epizod AOD pri zaposlenih. Pri osThe life expectancy has been increasing significantly in the last decades. People aged over 65 represented 17% of population of Slovenia and 5% of the elderly (about 19,500) resided in 96 long-term care facilities and nursing homes (NH). Ageing parallels with a decline of many functions and is accompanied by the increasing frequency of chronic illnesses, impaired mobility and the need for assistance in daily living. The inability to take care of oneself is a rather common reason for a decision to become a NH resident. Acute respiratory infections (ARI) are common among NH residents, representing about 1/3 of all infections, and are the most frequent reason for hospital admittance, and a significant cause of mortality. Nevertheless, the knowledge of infections with respiratory viruses in NH residents is incomplete. More information is available for the epidemic rather than for sporadic type of infections. Due to daily visitors and NH staff viral infections from the community can be introduced into the NH and affect residents with chronic illnesses, impaired consciousness, impaired mobility etc. In addition, scarce clinical symptoms combined with limited diagnostic facilities hamper the recognition of infections and consequently lead to delayed introduction of preventive measures.
Participants and methods
We accomplished a 6-months prospective surveillance study from 5 December 2011 to 31 May 2012 in a part of 208-bed three-floor NH in north-eastern Slovenia that encompassed 90 (43.3%) residents (i.e., 90/97 residents living in one of the sections of the NH), and 42/53 (79.2%) nursing care workers, who provided signed informed consent for participation. Nasopharyngeal swabs for virology studies were collected from all participants at the time of enrolment (5 December 2012) and at the end of the study (31 May 2012), as well as from each participant who developed ARI within the period of the study. Cases of ARI were defined according to McGeer criteria for infection surveillance in long-term care facilities. During the 6-months study period the detection of ARI was carried out daily by trained study nurses and the diagnosis was confirmed by a physician who conducted a physical examination in case of illness. Daily number of visitors (adults, schoolchildren and pre-school children, respectively) in each participant’s room was recorded during study period.
Real-time PCR and real-time RT-PCR were performed detecting influenza A/B, adenovirus, parainfluenza viruses 1, 2 and 3, human rhinoviruses, respiratory syncytial virus, human metapneumovirus, human coronaviruses, human bocavirus in nasopharyngeal swab samples. Results were statistically analysed using chi-square test, Fisher exact test. Correlations were expressed using the Kendall Tau coefficient. Multivariate Poisson regression model was used for estimating the influence of independent variables on ARI incidence-rate.
Results
During the 6-months observational period 100 episodes of ARI were observed, 56 among residents and 44 among staff. The calculated incidence rate was 3.8 ARI/ 1000 persons-days for residents and 5.9 ARI/ 1000 persons-days for staff members. The weekly incidence rate of ARI in NH residents correlated with the weekly ARI incidence rate in NH staff. Using a multivariate Poisson model for the number of ARI occurrences, including age, influenza vaccination, mobility of residents and chronic underlying diseases as explanatory variables and controlling the length of exposure, we estimated that the relative incidence-rate ratio of ARI for patients without dementia was 2.5 times larger than that for patients with dementiathe other covariates were not statistically significantly associated with the number of ARI episodes. Respiratory viruses were detected in 55 out of 100 ARI episodes (55%): in 34/56 (60.7%) episodes of ARI in residents and in 21/44 (47.7%) cases of ARI in staff. Of 56 NH residents with ARI 41 (73.5%) fulfilled criteria for lower respiratory trac
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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