OBJECTIVE: Secukinumab 150 mg has demonstrated significant improvement in signs and symptoms of ankylosing spondylitis (AS), with response rates sustained for up to 5 years. Here, we report end-of-study 3-year efficacy and safety results of secukinumab 150 and 300 mg from the MEASURE 3 study. METHODS: A total of 226 patients was randomized to intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous (s.c.) secukinumab 300/150 mg every 4 weeks or a matched placebo. At week 16, placebo patients were re-randomized to s.c. secukinumab 300/150 mg. Analysis at week 156 included patients initially randomized to secukinumab and those who switched from placebo to secukinumab at week 16 (any secukinumab 300/150 mg). Outcome measures at week 156 included Assessment of Spondyloarthritis International Society (ASAS) 20/40, Bath Ankylosing Spondylitis Disease Activity Index, ASAS partial remission (PR), ASAS 5/6, and Ankylosing Spondylitis Disease Activity Score-C-reactive protein inactive disease. RESULTS: The retention rates from weeks 16 to 156 were 80.5% and 80.9% in secukinumab 300 and 150 mg, respectively. ASAS 20/40 response rates at week 156 were 75.0%/56.5% and 68.2%/47.7% for secukinumab 300 and 150 mg, respectively. At week 156, response rates on more stringent clinical end points (eg, ASAS 40, ASAS-PR) were higher with the 300-mg dose, particularly in tumor necrosis factor (TNF)-inadequate responder (IR) patients. No new safety findings were observed. CONCLUSION: Secukinumab (300 and 150 mg) provided sustained improvements through 3 years in the signs and symptoms of active AS. Improvements with secukinumab 300 mg were numerically higher compared with the 150-mg dose for some higher hurdle end points and in TNF-IR patients. The safety profile of secukinumab was consistent with previous reports.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Secukinumab, an anti-interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) in two phase 3 studies (MEASURE 1 and MEASURE 2). Here, we present 52-week results from the MEASURE 3 study assessing the efficacy and safety of secukinumab 300 and 150 mg subcutaneous maintenance dosing, following an intravenous loading regimen. METHODS: A total of 226 patients were randomized to intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 300 mg (IV-300 mg) or 150 mg (IV-150 mg) every 4 weeks, or matched placebo. Patients in the placebo group were re-randomized to subcutaneous secukinumab at a dose of 300 or 150 mg at week 16. The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16 in the IV-300 mg or IV-150 mg versus placebo. Other endpoints assessed through week 52 included improvements in ASAS40, ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index, and ASAS partial remission responses, as well as the change from baseline in high-sensitivity C-reactive protein levels. Statistical analyses followed a predefined hierarchical hypothesis testing strategy to adjust for multiplicity of testing, with non-responder imputation used for binary variables and mixed-model repeated measures for continuous variables. RESULTS: The primary efficacy endpoint was met; the ASAS20 response rate was significantly greater at week 16 in the IV-300 mg (60.5%; P < 0.01) and IV-150 mg (58.1%; P < 0.05) groups versus placebo (36.8%). All secondary endpoints were met at week 16, except ASAS partial remission in the IV-150 mg group. Improvements achieved with secukinumab in all clinical endpoints at week 16 were also sustained at week 52. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period. During the entire treatment period, pooled incidence rates of Candida infections and grade 3-4 neutropenia were 1.8% for both of these adverse events in secukinumab-treated patients. CONCLUSIONS: Secukinumab (300 mg and 150 mg dose groups) provided rapid, significant and sustained improvement through 52 weeks in the signs and symptoms of patients with AS. The safety profile was consistent with previous reports, with no new or unexpected findings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02008916 . Registered on 8 December 2013. EUDRACT 2013-001090-24. Registered on 24 October 2013). The study was not retrospectively registered.

• MeSH
• ankylózující spondylitida farmakoterapie   MeSH
• antirevmatika aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• injekce subkutánní MeSH
• interleukin-17 antagonisté a inhibitory   MeSH
• intravenózní podání MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Isatuximab is an anti-CD38 monoclonal antibody approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone for relapsed or refractory multiple myeloma. This phase 3, open-label study compared the efficacy of isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple myeloma. METHODS: This was a prospective, randomised, open-label, parallel-group, phase 3 study done at 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients with relapsed or refractory multiple myeloma aged at least 18 years who had received one to three previous lines of therapy and had measurable serum or urine M-protein were eligible. Patients were randomly assigned (3:2) to isatuximab plus carfilzomib-dexamethasone (isatuximab group) or carfilzomib-dexamethasone (control group). Patients in the isatuximab group received isatuximab 10 mg/kg intravenously weekly for the first 4 weeks, then every 2 weeks. Both groups received the approved schedule of intravenous carfilzomib and oral or intravenous dexamethasone. Treatment continued until progression or unacceptable toxicity. The primary endpoint was progression-free survival and was assessed in the intention-to-treat population according to assigned treatment. Safety was assessed in all patients who received at least one dose according to treatment received. The study is registered at ClinicalTrials.gov, NCT03275285. FINDINGS: Between Nov 15, 2017, and March 21, 2019, 302 patients with a median of two previous lines of therapy were enrolled. 179 were randomly assigned to the isatuximab group and 123 to the control group. Median progression-free survival was not reached in the isatuximab group compared with 19·15 months (95% CI 15·77-not reached) in the control group, with a hazard ratio of 0·53 (99% CI 0·32-0·89; one-sided p=0·0007). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 136 (77%) of 177 patients in the isatuximab group versus 82 (67%) of 122 in the control group, serious TEAEs occurred in 105 (59%) versus 70 (57%) patients, and TEAEs led to discontinuation in 15 (8%) versus 17 (14%) patients. Fatal TEAEs during study treatment occurred in six (3%) versus four (3%) patients. INTERPRETATION: The addition of isatuximab to carfilzomib-dexamethasone significantly improves progression-free survival and depth of response in patients with relapsed multiple myeloma, representing a new standard of care for this patient population. FUNDING: Sanofi. VIDEO ABSTRACT.

• MeSH
• antiflogistika terapeutické užití   MeSH
• dexamethason terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunologické faktory terapeutické užití   MeSH
• intravenózní podání MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   MeSH
• oligopeptidy terapeutické užití   MeSH
• prospektivní studie MeSH
• recidiva MeSH
• senioři MeSH
• thalidomid analogy a deriváty   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Trauma-induced coagulopathy (TIC) substantially contributes to mortality in bleeding trauma patients. OBJECTIVE: The aim of the study was to administer fibrinogen concentrate in the prehospital setting to improve blood clot stability in trauma patients bleeding or presumed to bleed. DESIGN: A prospective, randomised, placebo-controlled, double-blinded, international clinical trial. SETTING: This emergency care trial was conducted in 12 Helicopter Emergency Medical Services (HEMS) and Emergency Doctors' vehicles (NEF or NAW) and four trauma centres in Austria, Germany and Czech Republic between 2011 and 2015. PATIENTS: A total of 53 evaluable trauma patients aged at least 18 years with major bleeding and in need of volume therapy were included, of whom 28 received fibrinogen concentrate and 25 received placebo. INTERVENTIONS: Patients were allocated to receive either fibrinogen concentrate or placebo prehospital at the scene or during transportation to the study centre. MAIN OUTCOME MEASURES: Primary outcome was the assessment of clot stability as reflected by maximum clot firmness in the FIBTEM assay (FIBTEM MCF) before and after administration of the study drug. RESULTS: Median FIBTEM MCF decreased in the placebo group between baseline (before administration of study treatment) and admission to the Emergency Department, from a median of 12.5 [IQR 10.5 to 14] mm to 11 [9.5 to 13] mm (P = 0.0226), but increased in the FC Group from 13 [11 to 15] mm to 15 [13.5 to 17] mm (P = 0.0062). The median between-group difference in the change in FIBTEM MCF was 5 [3 to 7] mm (P < 0.0001). Median fibrinogen plasma concentrations in the fibrinogen concentrate Group were kept above the recommended critical threshold of 2.0 g l-1 throughout the observation period. CONCLUSION: Early fibrinogen concentrate administration is feasible in the complex and time-sensitive environment of prehospital trauma care. It protects against early fibrinogen depletion, and promotes rapid blood clot initiation and clot stability. TRIAL REGISTRY NUMBERS: EudraCT: 2010-022923-31 and ClinicalTrials.gov: NCT01475344.

• MeSH
• dospělí MeSH
• fibrinogen * MeSH
• lidé MeSH
• mladiství MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• urgentní zdravotnické služby * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Česká republika MeSH
• Německo MeSH
• Rakousko MeSH

BACKGROUND: High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4-6 years after disease onset. METHODS: In this retrospective international observational study, we obtained data from the MSBase registry and the Swedish MS registry, which prospectively collect patient data that are specific to multiple sclerosis as part of routine clinical care. We identified adult patients (aged ≥18 years) with relapsing-remitting multiple sclerosis, with at least 6 years of follow-up since disease onset, and who started the high-efficacy therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab) either 0-2 years (early) or 4-6 years (late) after clinical disease onset. We matched patients in the early and late groups using propensity scores calculated on the basis of their baseline clinical and demographic data. The primary outcome was disability, measured with the Expanded Disability Status Score (EDSS; an ordinal scale of 0-10, with higher scores indicating increased disability), at 6-10 years after disease onset, assessed with a linear mixed-effects model. FINDINGS: We identified 6149 patients in the MSBase registry who had been given high-efficacy therapy, with data collected between Jan 1, 1975, and April 13, 2017, and 2626 patients in the Swedish MS Registry, with data collected between Dec 10, 1997, and Sept 16, 2019. Of whom, 308 in the MSBase registry and 236 in the Swedish MS registry were eligible for inclusion. 277 (51%) of 544 patients commenced therapy early and 267 (49%) commenced therapy late. For the primary analysis, we matched 213 patients in the early treatment group with 253 in the late treatment group. At baseline, the mean EDSS score was 2·2 (SD 1·2) in the early group and 2·1 (SD 1·2) in the late group. Median follow-up time for matched patients was 7·8 years (IQR 6·7-8·9). In the sixth year after disease onset, the mean EDSS score was 2·2 (SD 1·6) in the early group compared with 2·9 (SD 1·8) in the late group (p<0·0001). This difference persisted throughout each year of follow-up until the tenth year after disease onset (mean EDSS score 2·3 [SD 1·8] vs 3·5 [SD 2·1]; p<0·0001), with a difference between groups of -0·98 (95% CI -1·51 to -0·45; p<0·0001, adjusted for proportion of time on any disease-modifying therapy) across the 6-10 year follow-up period. INTERPRETATION: High-efficacy therapy commenced within 2 years of disease onset is associated with less disability after 6-10 years than when commenced later in the disease course. This finding can inform decisions regarding optimal sequence and timing of multiple sclerosis therapy. FUNDING: National Health and Medical Research Council Australia and MS Society UK.

• MeSH
• čas zasáhnout při rozvinutí nemoci MeSH
• databáze faktografické MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• posuzování pracovní neschopnosti MeSH
• registrace MeSH
• retrospektivní studie MeSH
• roztroušená skleróza terapie   MeSH
• tendenční skóre MeSH
• věk při počátku nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Švédsko MeSH

INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.

• MeSH
• biologické markery MeSH
• císařský řez MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• novorozenec MeSH
• placentární růstový faktor MeSH
• prediktivní hodnota testů MeSH
• preeklampsie * diagnóza   prevence a kontrola   epidemiologie   MeSH
• randomizované kontrolované studie jako téma MeSH
• receptor 1 pro vaskulární endoteliální růstový faktor MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

Cíl studie: Zjistit, jaké změny v reprodukčním zdraví žen vyvolaly změny v systému zdravotnípéče a v sociální sféře.V dílčí studii III analyzovat změny ve frekvenci umělého ukončení těhotenství (UUT), jako pod-klad pro jejich srovnání se změnami v používání antikoncepce.Typ studie: Retrospektivní srovnávací epidemiologická studie.Název a sídlo pracoviště: Ústav pro péči o matku a dítě, Praha-Podolí.Metodika: Za zdroj údajů byly použity údaje Ústavu zdravotnických informací a statistiky ČR.Kromě změn v absolutním počtu UUT byly tyto diferencovány podle mezinárodních kritérií„Abortion rate” a „Abortion ration”. Údaje byly korelovány s věkem ženy, rodinným stavem, úrov-ní dosaženého vzdělání a počtem narozených dětí.Výsledky: Od přijetí zákona o UUT až do r. 1991 byl každoročně kolísající počet UUT zrcadlovýmobrazem kolísajícího počtu porodů v důsledku měnící se fertility žen. Poté však začal s poklesemporodů současně klesat i počet UUT. Hodnoceno podle „Abortion ratio” došlo sice v období 1993 až1997 k jeho snížení ze 34,3 na 29,1 %, ale stále je to procento vyšší než ve vyspělých zemích. Podleukazatelů charakterizujících sociodemografické postavení ženy k největšímu poklesu počtu UUTdošlo u žen vdaných, se 2 narozenými dětmi a střední úrovní vzdělání. Podle počtu UUT na 1000žen k největšímu poklesu došlo sice rovněž u žen vdaných, ale též u žen 15-19letých a vysokoškola-ček, naopak k nejnižšímu u žen svobodných.Závěr: V dílčí studii III byly pomocí mezinárodních kritérií analyzovány změny v poklesu počtuUUT v období 1993 - 97, a to v souvislosti se 4 ukazateli charakterizujícími sociodemograficképostavení žen. Zjištěná data budou použita pro analýzu vývoje vztahu Antikoncepce/UUT v uvede-ném období, která je obsahem další dílčí studie.

Objective: To analyze the effect of changes in system of health and social care on reproductivehealth of women. In particular to analyze the changes in frequency of induced abortions asa basis for evaluation of changes in contraceptive use.Design: Retrospective comparative epidemiological study.Setting: Institute for the Care of Mother and Child, Praha 4 - Podolí.Methods: The database of the Czech Office of Health Statistics and Information was used. Besidescomparison of absolute numbers of induced abortions we used international criteria „Abortionrate” and „Abortion ratio”. These parameters were compared with maternal age, marital status,level of education, and number of children.Results: Since the legislature on induced abortions came into effect till 1991 the annual variationsof the number of induced abortions in the Czech Republic were inverse to changes in number ofbirths due to current fertility. However, since then the number of abortions has been decreasingwhile the number of births was also decreasing. Using the abortion ratio as a measure, we wereable to observe the decrease from 34.3 to 29.1 % during 1993 - 1997, however the later value is stillhigher than in developed world. According to the selected social-demographic parameters ofwomen we have seen the highest decrease of absolute number of abortions among married wo-men, women with two children, and women with secondary education. According to the numberof abortions per 1000 women of reproductive age there has also been decrease among marriedwomen, however also among women 15 - 19 year and among women with university education.The smallest decrease of abortion rate has been observed among single women.Conclusions: In this part of the study we analyzed the decrease of induced abortions during 1993 -1997 related to four selected social-demographic characteristics of women of reproductive age.Our results will be used for further analyses of relationship of contraception and induced aborti-ons during the specified period. Such analysis is a subject of separate study.

• MeSH
• dospělí MeSH
• epidemiologické studie MeSH
• indukovaný potrat statistika a číselné údaje   MeSH
• lidé MeSH
• porod MeSH
• reprodukční zdraví MeSH
• statistika jako téma MeSH
• těhotenství MeSH
• ženy MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

Práce je dílčím výsledkem projektu, jehož cílem byl vývoj a zavedení metodiky získávání a dlouhodobého skladování erytrocytů pro strategické, speciální a léčebné potřeby Armády České republiky a státu. Jako základní zkoumaná metoda bylo zvoleno mražení erytrocytů, získaných metodou dvojité erytrocytaferézy, ve vysoké koncentraci glycerolu při -85 °C a teplotě skladování -65 °C a nižší. Glycerolizace a deglycerolizace erytrocytů, včetně jejich závěrečné resuspenze v Nutricelu (AS-3), byla prováděna uzavřeným a automatizovaným systémem na zařízení Haemonetics ACP 215. Stabilita EAK rekonstituovaných v AS-3 byla ověřena jak klinickým hodnocením u zdravých dobrovolníků pomocí tzv. indexu terapeutické účinnosti, tak biochemickými a hematologickými parametry. Rekonstituované erytrocytární jednotky byly hodnoceny ve dnech 0, 7, 14 a 21 po rozmražení 51Cr značenými erytrocyty ve dvou skupinách: mražené a skladované v primárních vacích (skupina A) a mražené a skladované po přepuštění do speciálních vaků pro hluboké zmražení (skupina B). Bylo měřeno 24hodinové přežívání autologních erytrocytů podávaných zdravým dobrovolníkům a stanoven index terapeutické účinnosti (ITE) za pomoci tzv. freeze-thaw-wash-recovery (FTW%) závislého na množství hemoglobinu v odpadu po promytí rozmražených erytrocytů. Celkem bylo zmraženo, rekonstituováno a takto vyšetřeno 104 TU erytrocytů. Hodnocené erytrocyty v obou skupinách vykazují téměř shodné hodnoty ITE: 74,01 (±CI95 %: 71,97–76,04) a 74,02 (±CI95 %: 71,18–76,87) bez ohledu na délku sledované doby uchovávání po rekonstituci (21 dní). U skupiny B bylo zjištěno 4% snížení hodnoty přežití po 24 hod. a 4% zvýšení hodnoty FTW%. Hodnoty hemolýzy na konci doby skladování byly u všech hodnocených skupin nižší než 1 %. Z hematologických a biochemických parametrů byly sledovány změny hemoglobinu, hematokritu, leukocytů, hemolýzy, osmolality, pH, K, P, ATP, NH3 a 2,3-DPG. Také výsledky měření těchto laboratorních parametrů prokázaly dobrou použitelnost zmražených erytrocytů ještě 3 týdny po rozmražení, rekonstituci v Nutricelu a uchovávání při teplotě 2–6 °C.

The article summarised partial results the project of evaluation and implementation method for collection and longterm storage packed red cells (RBC) for strategic, special and therapeutic findings Army of Czech Republic as well as the country. The essential surveyed method was freezing of RBC collected by double erythrocytapheresis in high glycerol at -80 °C and stored at -65 °C and lower. Glycerolisation, deglycerolisation and resuspension in Nutricel (AS- 3) was performed with the Haemonetics ACP 215 machine by closed system. Stability of RBC in AS-3 was evaluated by clinical study with health volunteers by index of therapeutic effectiveness (ITE) as well as by biochemical and haematological parameters. Reconstituted RBC units were evaluated in days 0,7,47 and 21 after thawing by 51Cr labelled red cells in two groups: freezing and storage in primary collection bags (group A) and freeing and storage in special bags for deep freezing (group B). 24-hour survival autologous red cell at health volunteers were observed and set ITE and via “freeze-thaw-wash-recovery” (FTW%) dependent on amount of haemoglobin in waste after washing deglycerolised RBCs. Totally 104 RBC units were frozen, reconstituted and measured. Evaluated RBCs both groups were almost statistically identical ITE: 74.01 (±CI95%: 71.97–76.04), 74.02 (±CI95%: 71.18–76.87) and 74.5 (±CI95%: 71.62–77.38), respectively, regardless of storage time after RBCs deglycerolization. The 4-percent decrease of 24-hour posttransfusion survival (%) means as well as 4-percent increase of FTW% means were statistically significant between RBCs group B and A. Haemolysis in the end of storage was below 1% at both group. From haematological and biochemical parameters haemoglobin, haematocrit, leucocytes, haemolysis, osmolality, pH, potassium, phosphorus, ATP, ammoniac and 2,3-DPG were observed. Results of these tests demonstrate good applicability frozen RBC 3 week after thawing and reconstitution in Nutricel and following storage at 2–6 °C.

• Klíčová slova
• Nutricel,
• MeSH
• finanční podpora výzkumu jako téma MeSH
• konzervace krve metody   MeSH
• kryoprezervace metody   využití   MeSH
• lidé MeSH
• separace krevních složek metody   MeSH
• transfuze erytrocytů metody   MeSH
• vojenské lékařství MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• hodnotící studie MeSH

Cíl: Cílem studie je vyhodnotit opakovatelnost měření neinvazivního break-up time (NIBUT) keratografem při jeho stanovení z jednoho, dvou či třech dílčích měření a doporučit pro praxi vhodnou metodiku. Dalším cílem je ověřit, zda opakovaná měření neovlivňují měřenou hodnotu. Materiál a metodika: Do studie bylo zařazeno 38 zdravých dobrovolníků (30 žen a 8 mužů) ve věku od 19 do 50 let, u každého bylo měřeno vždy jen jedno oko. Studie byla koncipována jako prospektivní. Po 15minutové adaptaci na podmínky vyšetřovny podstoupil každý účastník dvě série měření NIBUT (test, retest) na keratografu OCULUS 3. Minimální časový odstup obou sérií byl 10 minut, každá série obsahovala tři dílčí měření v odstupu přibližně 3 minuty. Výsledný NIBUT byl v každé sérii stanoven (A) jako první hodnota v dané sérii, (B) jako průměr prvních dvou nebo (C) všech tří měření v dané sérii. Opakovatelnost byla hodnocena Bland-Altmanovou analýzou a vyjádřena koeficientem opakovatelnosti. Sledován byl vždy pouze čas prvního roztržení slzného filmu. Výsledky: Statistická analýza neprokázala statisticky signifikantní rozdíly jak mezi dílčími měřeními NIBUT v jednotlivých sérií (p = 0,92, p = 0,81), tak při porovnání všech šesti měření (p = 0,95). Průměrné hodnoty dílčích měření se pohybovaly od 13,6 s do 14,4 s. Pro postupy A, B a C byly zjištěny koeficienty opakovatelnosti (po řadě) 15,0 s, 12,1 s a 10,0 s. Doplňující analýza pro 12 očí s nízkým NIBUT (< 10 s) prokázala statisticky signifikantně lepší opakovatelnost v této skupině, a to s koeficienty 7,0 s (metodika A), 6,0 s (B) a 4,6 s (C) . Závěr: Stanovení NIBUT ze tří po sobě jdoucích měření (s dostatečným, ideálně několikaminutovým odstupem) významně zlepšuje opakovatelnost. Přitom takto opakovaná měření NIBUT nemají významný vliv na měřenou hodnotu. Uvedenou metodiku měření NIBUT na keratografu lze doporučit pro použití v praxi.

Aim: The primary aim of this study is to evaluate the repeatability of noninvasive break-up time (NIBUT) measurement by keratograph when it is determined from one, two or three partial measurements, and to recommend a suitable methodology for practice. Another goal is to verify that repeated measurements do not affect the measured value. Material and Methods: Thirty-eight healthy volunteers (30 women and 8 men) aged between 19 and 50 years old were included in the study, in which only one eye of each volunteer was measured. The study was designed as a prospective one. Each subject adapted to the local conditions of the laboratory for 15 minutes and subsequently underwent two series of NIBUT measurements (test, retest) on an OCULUS 3 Keratograph. The minimum time interval between the two series was 10 minutes, in which each series contained three partial measurements approximately 3 three measurements in the given series. Repeatability was assessed by a Bland-Altman analysis and expressed as a repeatability coefficient. In every case, only the time of the first break-up of the tear film was monitored. Results: The statistical analysis did not show statistically significant differences both between partial measurements of NIBUT in the individual series (p = 0.92, p = 0.81) and when comparing all six measurements (p = 0.95). The mean values of the partial measurements ranged from 13.6 s to 14.4 s. The repeatability coefficients were found to be 15.0 s, 12.1 s and 10.0 s for methodologies A, B and C, respectively. A supplementary analysis for 12 eyes with low NIBUT (< 10 s) showed statistically significantly better repeatability in this group, with coefficients of 7.0 s (methodology A), 6.0 s (B) and 4.6 s (C). Conclusion: Determination of NIBUT from three consecutive measurements (with a sufficient interval of ideally a few minutes) significantly improves repeatability. Such repeated NIBUT measurements do not have a significant effect on the measured value. The mentioned methodology for measuring NIBUT on a keratograph can be recommended for use in practice.

• Klíčová slova
• slzný film, break-up time test, opakovatelnost měření, keratograf OCULUS 3,
• MeSH
• diagnostické techniky oftalmologické * klasifikace   přístrojové vybavení   MeSH
• prospektivní studie MeSH
• rohovka diagnostické zobrazování   fyziologie   patologie   MeSH
• syndromy suchého oka * diagnostické zobrazování   diagnóza   MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010-11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet). METHODS: We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012-2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose. RESULTS: The PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0-88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8-96.1) < 12 months to 85.1% (72.0-92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7-94.7) against fatal PCV13 IPD, 64.5% (43.7-77.6), 83.2% (73.7-89.3) and 85.1% (67.6-93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3-94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4-92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2-96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and -14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively. CONCLUSIONS: PCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.

• MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• očkovací schéma MeSH
• pneumokokové infekce * epidemiologie   prevence a kontrola   MeSH
• pneumokokové vakcíny MeSH
• séroskupina MeSH
• Streptococcus pneumoniae * MeSH
• vakcíny konjugované MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH