Východiska: U nemocných s diabetes mellitus (DM) 2. typu a u nemocných s mírným srdečním selháním (SS) s i bez DM snižují inhibitory sodíko-glukózového kotransportéru 2 (SGLT2) závažné příhody SS. Jsou potřeba další důkazy pro SGLT2 inhibitory pro nemocné se SS, především u těch s významně sníženou ejekční frakcí a se zvýšenými natriuretickými peptidy bez ohledu na přítomnost DM. Metodika: Jednalo se o studii fáze III, kdy bylo randomizováno 3 730 nemocných NYHA II, III a IV s ejekční frakcí < 40, aby dostali empagliflozin 10 mg denně nebo placebo k jejich doporučené medikaci. Primární kombinovaný cíl byl kardiovaskulární úmrtí a hospitalizace pro zhoršení SS. Dalším sekundárním cílem bylo ovlivnění renálních funkcí. Výsledky: Průměrná doba sledování byla 16 měsíců a po tuto dobu byl primární cíl u 361 nemocných z 1 863 (19,4 %) na empagliflozinu a u 462 z 1 867 nemocných (24,7 %) na placebu (p < 0,001). Efekt empagliflozinu na primární cíl byl stejný u nemocných s i bez DM a u nemocných léčených či neléčených sakubitril/valsartanem. Především byl empagliflozinem snížen počet hospitalizací (p < 0,001). Snížení glomerulární filtrace bylo taktéž nižší na empagliflozinu než na placebu (–0,2 ml/min/1,73 m2/rok vs. –2,3 ml/min/1,73 m2/rok; p < 0,001) a byl doprovázen menším počtem nežádoucích renálních příhod. Výskyt hypotenze, renální dysfunkce či hypoglykemie byl v obou skupinách stejný. Závěr: Mezi širokým spektrem nemocných se SS se sníženou ejekční frakcí snižuje empagliflozin riziko kardiovaskulárních úmrtí a hospitalizací pro SS, bez ohledu na přítomnost DM.

Background: In patients with type 2 diabetes and in those with primarily mild heart failure with and without diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of serious heart failure (HF) events. More evidence is needed regarding the effects of SGLT2 inhibitors in patients across the broad spectrum of HF, including those with markedly reduced ejection fraction and higher natriuretic peptide levels, regardless of the presence of diabetes. Methods: In this phase III, placebo-controlled trial, we randomly assigned 3,730 patients with New York Heart Association class II, III, or IV HF and an ejection fraction of 40 % or less to receive either empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes and hospitalization for worsening heart failure. Another secondary enpoint was effect on renal functions. Results: Over a median of 16 months, the primary outcome occurred in 361 of 1,863 patients (19.4%) in the empagliflozin group and in 462 of 1,867 patients (24.7%) in the placebo group (HR 0.75; 95% CI, 0.65 to 0.86; P<0.001). The effect of empagliflozin on the primary outcome was consistent in patients with and without diabetes and in those taking and not taking sacubitril/valsartan. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (HR 0.70; 95% CI, 0.58 to 0.85; P<0.001). The rate of decline in eGFR was slower in the empagliflozin group than in the placebo group (–0.2 ml/min/1.73m2/year vs. –2.3 ml/min/1.73m2/year; P < 0.001), and was accompanied by a lower frequency of serious renal outcomes. The frequency of adverse events related to hypotension, renal dysfunction and hypoglycemia did not differ between treatment groups. Conclusions: Among a broad spectrum of patients with HF and a reduced ejection fraction, empagliflozin reduced the risk of death from cardiovascular causes or hospitalization for HF, regardless of the presence or absence of diabetes and background therapy for HF.

• Klíčová slova
• EMPAGLIFLOZIN,
• MeSH
• diabetes mellitus farmakoterapie   MeSH
• glifloziny terapeutické užití   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• srdeční selhání * farmakoterapie   MeSH
• Check Tag
• lidé MeSH

Pozadí: U nemocných se srdečním selháním s i bez diabetes mellitus inhibitory sodíkoglukózového kotransportéru 2 (SGLT2) inhibitory snižují závažné příhody srdečního selhání. Jsou potřeba další důkazy pro SGLT2 inhibitory pro nemocné se srdečním selháním, především u těch s významně sníženou ejekční frakcí a se zvýšenými natriuretickými peptidy. Metodika: Jednalo se o studii fáze III, kdy bylo randomizováno 3 730 nemocných NYHA II, III a IV s ejekční frakcí pod 40 %, aby dostali empagliflozin 10 mg denně nebo placebo k jejich doporučené medikaci. Primární kombinovaný cíl byl kardiovaskulární úmrtí a hospitalizace pro zhoršení srdečního selhání. Dalším sekundárním cílem bylo ovlivnění renálních funkcí. Výsledky: Průměrná doba sledování byla 16 měsíců a po tuto dobu byl primární cíl u 361 nemocných z 1 863 (19,4 %) na empa-gliflozinu a u 462 z 1 867 nemocných (24,7 %) na placebu (p < 0,001). Efekt empagliflozinu na primární cíl byl stejný u nemocných s i bez diabetes mellitus a u nemocných léčených či neléčených sacubitril valsartanem. Především byl empagliflozinem snížen počet hospitalizací (p < 0,001). Snížení glomerulární filtrace bylo taktéž nižší na empagliflozinu než na placebu. Výsk y t hypotenze, renální dysfunkce či hypoglykemie byl v obou skupinách stejný.Závěr: Mezi širokým spektrem nemocných se srdečním selháním a sníženou ejekční frakcí empagliflozin snižuje riziko kardiovaskulárních úmrtí a hospitalizací pro srdeční selhání, bez ohledu na přítomnost diabetes mellitus.

Background: In patients with heart failure with and without diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of serious heart failure events. More evidence is needed regarding the effects of SGLT2 inhibitors in patients across the broad spectrum of heart failure, including those with markedly reduced ejection fraction and higher natriuretic peptide levels. Methods: In this phase III, placebo-controlled trial, we randomly assigned 3,730 patients with New York Heart Association class II, III, or IV heart fail-ure and an ejection fraction of 40 % or less to receive either empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes and hospitalization for worsening heart failure. A secondary endpoint was effect on renal functions. Results: Over a median of 16 months, the primary outcome occurred in 361 of 1,863 patients (19.4 %) in the empagliflozin group and in 462 of 1,867 patients (24.7 %) in the placebo group (hazard ratio, 0.75; 95 % confidence interval [CI], 0.65 to 0.86; P < 0.001). The effect of empagliflozin on the primary outcome was consistent in patients with and without diabetes and in those taking and not taking sacubitril/valsartan. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.70; 95 % CI, 0.58 to 0.85; P < 0.001). The rate of decline in eGFR was slower in the empagliflozin group than in the placebo group. The frequency of adverse events related to hypotension, renal dysfunction, and hypoglycemia did not differ between the treatment groups. Conclusions: Across a broad spectrum of patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk of death from cardiovascular causes or hospitalization for heart failure, regardless of the presence or absence of diabetes and background therapy for heart failure.

• MeSH
• benzhydrylové sloučeniny terapeutické užití   MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• glukosidy * terapeutické užití   MeSH
• komplikace diabetu farmakoterapie   prevence a kontrola   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• renální insuficience prevence a kontrola   MeSH
• srdeční selhání * farmakoterapie   MeSH
• transportér 2 pro sodík a glukózu * MeSH
• Check Tag
• lidé MeSH

The decline of the production of several hormones with age has been recently linked to several degenerative processes related to aging including osteoporosis. The aim of our study was to confirm the observations published in 1994 suggesting that postmenopausal women with DHEAS levels below a certain limit have a much higher risk of osteoporosis than those with the levels above this limit. The DHEAS levels were measured by RIA and compared to our own age-adjusted reference ranges. Ihe values lower than 25th quantile were considered „subnormal". More than 500 postmenopausal subjects were included in our study. In those with „subnormal" levels bone mineral density (BMD) was measured on DEXA (Lunar or Hologic). Decreased BMD ranging from osteopenia to severe osteoporosis was found in 86 % of 74 women with „subnormal" DHEAS, while the expected frequency in our postmenopausal population may be about 30 %. In the following period the serum DHEAS levels were compared with DEXA findings in another 134 postmenopausal women. The DHEAS levels in all stages of decreased BMD were significantly lower than those in the group with normal BMD. The clinical sensitivity and specificity of DHEAS as a marker of increased risk of osteoporosis has been calculated for a cut-off limit of 0.5 MoM. In the light of these findings we believe that the robust and relatively cheap DHEAS determination could help us to identify women who are at higher risk of osteoporosis. Also, in the future, only the women with evidently deficient DHEA production might possibly become candidates for eventual DHEA substitution.

• MeSH
• dehydroepiandrosteron krev   nedostatek   MeSH
• dospělí MeSH
• kostní denzita MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteoporóza krev   MeSH
• postmenopauza MeSH
• referenční hodnoty MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH

Pozadí: U nemocných se srdečním selháním s i bez diabetes mellitus inhibitory sodíko­glukozového kotransportéru 2 (SGLT­2) inhibitory snižují závažné příhody srdečního selhání. Jsou potřeba další důkazy pro SGLT­2 inhibitory pro nemoc­né se srdečním selháním, především u těch s významně sníženou ejekční frakcí a se zvýšenými natriuretickými peptidy.Metodika: Jednalo se o studii fáze III, kdy bylo randomizováno 3 730 nemocných NYHA II, III a IV s ejekční frakcí pod 40 %, aby dostali empagliflozin 10 mg denně nebo placebo k jejich doporučené medikaci. Primární kombinovaný cíl byl kardiovaskulární úmrtí a hospitalizace pro zhoršení srdečního selhání. Dalším sekundárním cílem bylo ovlivnění renálních funkcí.Výsledky: Průměrná doba sledování byla 16 měsíců a po tuto dobu byl primární cíl u 361 nemocných z 1863 (19,4 %) na empagliflozinu a u 462 z 1 867 nemocných (24,7 %) na placebu (p < 0,001). Efekt empagliflozinu na primární cíl byl stejný u nemocných s i bez diabetes mellitus a u nemocných léčených či neléčených sacubitril valsartanem. Především byl empagliflozinem snížen počet hospitalizací (p < 0,001). Snížení glomerulární filtrace bylo taktéž nižší na empagliflozinu než na placebu. Výskyt hypotenze, renální dysfunkce či hypoglykemie byl v obou skupinách stejný.Závěr: Mezi širokým spektrem nemocných se srdečním selháním a sníženou ejekční frakcí empagliflozin snižuje riziko kardiovaskulárních úmrtí a hospitalizací pro srdeční selhání, bez ohledu na přítomnost diabetes mellitus.

Background: In patients with heart failure with and without diabetes, inhibitors of sodium­glucose cotransporter 2 (SGLT­2) reduce the risk of serious heart failure events. More evidence is needed regarding the effects of SGLT­2 inhibitors in patients across the broad spectrum of heart failure, including those with markedly reduced ejection fraction and higher natriuretic peptide levels,.Methods: In this phase III, placebo­controlled trial, we randomly assigned 3 730 patients with New York Heart Associati­on class II, III, or IV heart failure and an ejection fraction of 40 % or less to receive either empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes and hospitalization for worsening heart failure. Another secondary enpoint was effect on renal functions.Results: Over a median of 16 months, the primary outcome occurred in 361 of 1863 patients (19,4 %) in the empagli­flozin group and in 462 of 1 867 patients (24,7 %) in the placebo group (hazard ratio, 0,75; 95% confidence interval [CI], 0,65 to 0,86; p < 0,001). The effect of empagliflozin on the primary outcome was consistent in patients with and without diabetes and in those taking and not taking sacubitril/valsartan. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0,70; 95% CI, 0,58 to 0,85; p < 0,001). The rate of decline in eGFR was slower in the empagliflozin group than in the placebo group. The frequency of adverse events related to hypotension, renal dysfunction and hypoglycemia did not differ between treatment groups.Conclusions: Among a broad spectrum of patients with heart failure and a reduced ejection fraction, empagliflozin redu­ced the risk of death from cardiovascular causes or hospitalization for heart failure, regardless of the presence or absence of diabetes and background therapy for heart failure.

• Klíčová slova
• studie EMPEROR-REDUCED,
• MeSH
• dospělí MeSH
• glifloziny * terapeutické užití   MeSH
• klinické zkoušky, fáze III jako téma * MeSH
• lidé MeSH
• systolické srdeční selhání farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• komentáře MeSH

Patients connected to a high-frequency oscillatory ventilator should be paralysed or highly sedated so that the ventilator is able to work. Th e aim of the study is to design a special “Demand Flow System” allowing spontaneous breathing in patients ventilated using a high-frequency ventilator. Th e principle of the device is a fast and exact monitoring of pressure in the ventilatory circuit, followed by a separation of the pressure signal components generated by the oscillatory ventilator and by patient’s breathing activity. Th e latest mentioned signal is used for a real-time control of the extra fl ow injected into the ventilatory circuit so that the extra fl ow could compensate the pressure changes generated by the patient. Th e system reduces imposed work of breathing by 80 % and it allows spontaneous breathing during high-frequency oscillatory ventilation.

• MeSH
• dýchání MeSH
• experimenty na zvířatech MeSH
• financování organizované MeSH
• mechanické ventilátory trendy   využití   MeSH
• mechanika dýchání fyziologie   MeSH
• modely u zvířat MeSH
• plicní ventilace fyziologie   MeSH
• prasata MeSH
• vysokofrekvenční ventilace metody   přístrojové vybavení   využití   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

The mammalian magnetic sense is predominantly studied in species with reduced vision such as mole-rats and bats. Far less is known about surface-dwelling (epigeic) rodents with well-developed eyes. Here, we tested the wood mouse Apodemus sylvaticus for magnetoreception using a simple behavioural assay in which mice are allowed to build nests overnight in a visually symmetrical, circular arena. The tests were performed in the ambient magnetic field or in a field rotated by 90°. When plotted with respect to magnetic north, the nests were bimodally clustered in the northern and southern sectors, clearly indicating that the animals used magnetic cues. Additionally, mice were tested in the ambient magnetic field with a superimposed radio frequency magnetic field of the order of 100 nT. Wood mice exposed to a 0.9 to 5 MHz frequency sweep changed their preference from north-south to east-west. In contrast to birds, however, a constant frequency field tuned to the Larmor frequency (1.33 MHz) had no effect on mouse orientation. In sum, we demonstrated magnetoreception in wood mice and provide first evidence for a radical-pair mechanism in a mammal.

• MeSH
• čití, cítění fyziologie   MeSH
• elektromagnetické záření MeSH
• hnízdění fyziologie   MeSH
• magnetické pole * MeSH
• Murinae fyziologie   MeSH
• orientace fyziologie   MeSH
• rádiové vlny MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

BACKGROUND: Appetite and gastrointestinal hormones (GIHs) participate in energy homeostasis, feeding behavior and regulation of body weight. We demonstrated previously the superior effect of a hypocaloric diet regimen with lower meal frequency (B2) on body weight, hepatic fat content, insulin sensitivity and feelings of hunger compared to the same diet divided into six smaller meals a day (A6). Studies with isoenergetic diet regimens indicate that lower meal frequency should also have an effect on fasting and postprandial responses of GIHs. The aim of this secondary analysis was to explore the effect of two hypocaloric diet regimens on fasting levels of appetite and GIHs and on their postprandial responses after a standard meal. It was hypothesized that lower meal frequency in a reduced-energy regimen leading to greater body weight reduction and reduced hunger would be associated with decreased plasma concentrations of GIHs: gastric inhibitory peptide (GIP), glucagon-like peptide-1(GLP-1), peptide YY(PYY), pancreatic polypeptide (PP) and leptin and increased plasma concentration of ghrelin. The postprandial response of satiety hormones (GLP-1, PYY and PP) and postprandial suppression of ghrelin will be improved. METHODS: In a randomized crossover study, 54 patients suffering from type 2 diabetes (T2D) underwent both regimens. The concentrations of GLP-1, GIP, PP, PYY, amylin, leptin and ghrelin were determined using multiplex immunoanalyses. RESULTS: Fasting leptin and GIP decreased in response to both regimens with no difference between the treatments (p = 0.37 and p = 0.83, respectively). Fasting ghrelin decreased in A6 and increased in B2 (with difference between regimens p = 0.023). Fasting PP increased in B2with no significant difference between regimens (p = 0.17). Neither GLP-1 nor PYY did change in either regimen. The decrease in body weight correlated negatively with changes in fasting ghrelin (r = -0.4, p<0.043) and the postprandial reduction of ghrelin correlated positively with its fasting level (r = 0.9, p<0.001). The postprandial responses of GIHs and appetite hormones were similar after both diet regimens. CONCLUSIONS: Both hypocaloric diet regimens reduced fasting leptin and GIP and postprandial response of GIP comparably. The postprandial responses of GIHs and appetite hormones were similar after both diet regimens. Eating only breakfast and lunch increased fasting plasma ghrelin more than the same caloric restriction split into six meals. The changes in fasting ghrelin correlated negatively with the decrease in body weight. These results suggest that for type 2 diabetic patients on a hypocaloric diet, eating larger breakfast and lunch may be more efficient than six smaller meals during the day.

• MeSH
• časové faktory MeSH
• diabetes mellitus 2. typu dietoterapie   patologie   patofyziologie   psychologie   MeSH
• dospělí MeSH
• ghrelin krev   MeSH
• glukagonu podobný peptid 1 krev   MeSH
• hlad fyziologie   MeSH
• inzulinová rezistence MeSH
• jídla * fyziologie   psychologie   MeSH
• kalorická restrikce metody   MeSH
• klinické křížové studie MeSH
• leptin krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pankreatický polypeptid krev   MeSH
• peptid YY krev   MeSH
• senioři MeSH
• tělesná hmotnost MeSH
• výsledek terapie MeSH
• žaludeční inhibiční polypeptid krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Adverse events induced by intravesical bacillus Calmette-Guérin (BCG) to treat high-grade non-muscle-invasive bladder cancer (NMIBC) often lead to treatment discontinuation. The EAU-RF NIMBUS trial found a reduced number of standard-dose BCG instillations to be inferior with the standard regimen. Nonetheless, it remains important to evaluate whether patients in the reduced BCG treatment arm had better quality of life (QoL) due to a possible reduction in toxicity or burden. OBJECTIVE: To evaluate whether patients in the EAU-RF NIMBUS trial experienced better QoL after a reduced BCG instillation frequency. DESIGN SETTING AND PARTICIPANTS: A total of 359 patients from 51 European sites were randomized to one of two treatment arms between December 2013 and July 2019. The standard frequency arm (n = 182) was 6 weeks of BCG induction followed by 3 weeks of maintenance at months 3, 6, and 12. The reduced frequency arm (n = 177) was BCG induction at weeks 1, 2, and 6, followed by maintenance instillations at weeks 1 and 3 of months 3, 6, and 12. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Analyses were performed using an intention-to-treat analysis and a per-protocol analysis. QoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 version 3.0 (QLQ-C30 v.03) prior to the first and last instillations of each BCG cycle. Group differences were determined using linear regression corrected for QoL at baseline. Differences in QoL over time were tested for significance using a linear mixed model. Side effects were recorded by the treating physician using a standardized form. Chi-square tests were used to compare the side-effect frequency between the arms. RESULTS AND LIMITATIONS: There were no significant differences in the means of each QoL scale between the two arms. There were also no significant changes over time in all QoL domains for both arms. However, differences in the incidence of general malaise at T1 (before the last induction instillation), frequency, urgency, and dysuria at T7 (before the last maintenance instillation) were detected in favor of the reduced frequency arm. CONCLUSIONS: Reducing the BCG instillation frequency does not improve the QoL in NMIBC patients despite lower storage symptoms. PATIENT SUMMARY: In this study, we evaluated whether a reduction in the number of received bacillus Calmette-Guérin instillations led to better quality of life in patients with high-grade non-muscle-invasive bladder cancer. We found no difference in the quality of life between the standard and the reduced bacillus Calmette-Guérin instillation frequency. We conclude that reducing the number of instillations does not lead to better quality of life in patients with high-grade non-muscle-invasive bladder cancer.

• Publikační typ
• časopisecké články MeSH

Involvement of genetic factors in the aetiology of inflammatory bowel disease (IBD) has been known for a long time. Our aim was to investigate the prevalence of polymorphisms in NOD2, ICAM-1 and CCR5 genes in Czech and Slovak patients with IBD in comparison with healthy controls. The frequency of well-known mutations (R702W, G908W and 1007fs in the NOD2 gene; K469E in the ICAM-1 gene, and Delta32 in the CCR5 gene) involved in IBD was tested in 45 patients with CD and 22 patients with UC. The allele frequency of these mutations was determined and genotype-phenotype correlation was specified. Isolated DNA was genotyped, and allele frequency was counted and statistically verified. Significant differences between the healthy control group and CD patients were observed in mutation 1007fs of the NOD2 gene (P = 0.0203). We also associated allele E469 of the ICAM-1 gene with CD (P = 0.0024). No significant association between other alleles and CD was found, and no gene variation was linked to UC. The number of mutations and mutated genes was higher among patients with CD than among patients with UC. Our results support previous findings about participation of mutations of NOD2 and ICAM-1 genes in IBD. We confirmed that both CD and UC are polygenic diseases with a genedosage effect. This observation strengthens the opinion that genetic factors play a more important role in CD than in UC.

• MeSH
• Crohnova nemoc genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezibuněčná adhezivní molekula-1 genetika   MeSH
• mutace MeSH
• receptory CCR5 genetika   MeSH
• signální adaptorový protein Nod2 genetika   MeSH
• ulcerózní kolitida genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

BACKGROUND AND AIMS: Vedolizumab was shown to be safe and effective for the treatment of Crohn's disease [CD] and ulcerative colitis [UC] in the GEMINI Long-Term Safety [LTS] study. The vedolizumab Extended Access Program [XAP] provides patients with continued treatment. This XAP pharmacokinetics [PK] sub-study investigated vedolizumab efficacy, safety, and PK. METHODS: Vedolizumab dosing frequency was reduced from every 4 weeks [Q4W] to every 8 weeks [Q8W] at XAP enrolment, and patients were followed for 56 weeks. Outcomes included: efficacy, loss of clinical benefit, and re-escalation to Q4W dosing; and vedolizumab PK, immunogenicity, and adverse events. RESULTS: Among 167 enrolled patients [CD = 88, UC = 79], 80 [91%] with CD and 73 [92%] with UC completed 56 weeks; 76 [86%] and 71 [90%] with CD and UC, respectively, remained on Q8W dosing for 56 weeks. Clinical remission, corticosteroid-free clinical remission, and C-reactive protein levels were stable among patients remaining on Q8W through Week 56. Four patients with CD and two with UC resumed Q4W dosing [three with CD regained clinical response]. Patients with CD who completed Week 56 on Q8W dosing had median trough vedolizumab concentrations of 43.6 µg/mL at enrolment and 10.4 µg/mL at Week 56; concentrations were 42.4 µg/mL and 13.3 µg/mL, respectively, in patients with UC. Treatment-related adverse events were infrequent; no new or serious adverse events related to vedolizumab were reported. CONCLUSIONS: In the XAP-PK sub-study, adherence to Q8W dosing was high, with no loss of efficacy; very few patients required re-escalation to Q4W. There were no new safety signals.

• MeSH
• Crohnova nemoc * diagnóza   farmakoterapie   imunologie   MeSH
• dospělí MeSH
• gastrointestinální látky aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• imunologická odpověď na dávku MeSH
• integriny antagonisté a inhibitory   MeSH
• intravenózní infuze MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• ulcerózní kolitida * diagnóza   farmakoterapie   imunologie   MeSH
• vysazování léků metody   MeSH
• výsledky a postupy - zhodnocení (zdravotní péče) MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze IV MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH