Úvod: Stárnutí populace vede ke zvýšení počtu seniorů s poklesem fyzické zdatnosti a funkčními deficity. Aktivní intervence ve formě cílené fyzické aktivity k udržení celkové zdatnosti je nejvhodnější zahájit již ve fázi klesající zdatnosti, před rozvinutím plné křehkosti a disability seniorů. Jedním z nástrojů pro hodnocení fyzické výkonnosti, resp. křehkosti ve stáří je „Short Physical Performance Battery“ – SPPB. Cílem práce bylo zavedení této vyšetřovací baterie do klinické praxe v ČR a ověření vybraných psychometrických charakteristik. Metoda: Poprvé v České republice jsme použili „Krátkou baterii pro hodnocení fyzické zdatnosti seniorů“. Originální anglická verze SPPB byla přeložena do českého jazyka a zpět do jazyka anglického k zajištění jazykové přesnosti. SPPB byl aplikován na výběrovém souboru starších nemocných a validizován oproti běžně užívaným výkonovým testům kognice, sebeobsluhy a nutričního stavu. Výsledky: Při vyšetření 145 osob (108 žen, tj.74,5 %, a 37 mužů, tj. 25,5 % souboru) průměrného věku 80,3 (54–101 let, SD ? 8,5) jsme zjistili dobrou fyzickou zdatnost u 35 (24,1 %) osob (SPPB 10–12 bodů), 21 osob (14,5 %) disponovalo sníženou fyzickou zdatností (tzv. „pre‑frail“, SPPB 7–9 bodů) a 89 osob bylo zařazeno do kategorie křehkých seniorů s nízkou fyzickou zdatností a s vysokým rizikem budoucí nesoběstačnosti nebo již přítomnou disabilitou (SPPB ≤ 6 bodů). Celkové skóre SPPB statisticky významně korelovalo se stavem výživy (Mini‑Nutritional Assessment test – krátká verze, MNA‑SF), soběstačností v základní sebeobsluze (Activities of Daily Living – ADL) a kognitivním výkonem (Mini Mental State Examination – MMSE) – (korelace podle Spearmana: ρ = 0,51; 0,53 a 0,38). Při hodnocení podle 3 věkových kategorií [≤ 75 let (n = 41), 76–85 let (n = 62) a 86–101 let věku (n = 42)] byla korelace SPPB s MNA‑SF, ADL a MMSE nejvyšší u nejmladší věkové skupiny a se stoupajícím věkem klesala. V testu vnitřní konzistence jednotlivých položek SPPB dosáhlo Cronbachovo a hodnoty 0,821, což svědčí o vysokém stupni vnitřní konzistence vyšetřovací baterie. Závěr: Prokázali jsme vysokou korelaci testu SPPB s nutričním stavem, soběstačností a kognitivním výkonem ve sledovaném souboru a velmi dobrou vnitřní konzistenci testovací baterie. Baterii SPPB lze využít v klinické praxi k identifikaci seniorů s rizikem rozvoje syndromu geriatrické křehkosti a již rozvinutým klinickým fenotypem křehkosti. Pro svou jednoduchost, časovou i materiálovou nenáročnost je vhodná pro vyšetření ambulantních i hospitalizovaných seniorů, kteří mohou profitovat z intervenčních programů.

Introduction: Population ageing increases number of seniors with decline of physical capabilities and functional deficits. Targeted interventions to maintain or increase physical performance are most effective before the development of full frailty, in so-called „pre‑frail“ period. One of the assessment tools for evaluation of the physical performance and/or frailty in older persons is the „Short Physical Performance Battery“ – SPPB. The aim of the study was to introduce the assessment battery to clinical practice in the CR and to evaluate its selected psychometric properties. Method: Original English SPPB was translated into Czech language and back translated to ensure linguistic accuracy. SPPB was applied in the selected sample of older persons and validated against other performance tools for cognition, self-care and nutrition status used in CR and selected psychometric properties evaluated. Results: We examined 145 older persons (108 women, i.e. 74.48 % and 37 men, i.e. 25.52 %) mean age 80.38 years (54–101 years, SD ? 8,47). We found good physical performance in 35 (24.1 %) older persons (SPPB 10–12 points), 21 (14.5 %) were identified as pre‑frail (SPPB 7–9 points) and 89 (61.4 %) as frail in high risk of future disability or already disabled (SPPB ≤ 6 points). We found statistically significant correlation of global SPPB score with nutritional status (MNA-Short Form), activities of daily living performance (ADL) and cognitive performance (MMSE) – (Spearman correlation ρ = 0.51; 0.53 and 0.38 respectively). The Cronbach’s a for SPPB variables scored 0.821, which is consistent with good internal consistency of SPPB battery. When evaluating 3 age groups [≤ 75 years (n = 41), 76–85 (n = 62) and 86–101 years (n = 42)] the most significant correlations were found between SPPB and MNA, ADL and MMSE in the young elderly (ρ = 0.74, 0.79 and 0.64 respectively) and they diminished with increasing age. Conclusion: We confirmed significant correlations between SPPB and self care activities, cognitive performance and nutritional status and good internal consistency of the battery. SPPB test is simple, easy to perform, with low time and cost requirements. It could be recommended for clinical practice in both community and hospitalized older patients to evaluate their overall physical performance and identify persons at risk of frailty and disability who may profit from targeted interventions.

• MeSH
• chůze * MeSH
• geriatrické hodnocení * MeSH
• křehký senior MeSH
• lidé středního věku MeSH
• lidé MeSH
• péče o sebe MeSH
• pilotní projekty MeSH
• pohybová aktivita * MeSH
• posturální rovnováha MeSH
• reprodukovatelnost výsledků MeSH
• sarkopenie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stárnutí * MeSH
• statistika jako téma MeSH
• tělesná výkonnost * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH

In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤ 10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n = 101) or placebo (n = 103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n = 41; placebo, n = 47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs.

• MeSH
• antitumorózní látky škodlivé účinky   terapeutické užití   MeSH
• cyklické peptidy škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• nádory slinivky břišní farmakoterapie   MeSH
• neuroendokrinní nádory farmakoterapie   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• somatostatin škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• střevní nádory farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

OBJECTIVE: To evaluate if facial type is a predictor of the development of gingival recession. METHODS: A cohort of 179 orthodontic patients (76 males, 101 females; age before treatment T S = 12.4 years, SD = 0.8) were followed until 5 years post-treatment (T 5 = 20.7 years, SD = 1.2). The presence of recessions was scored ('Yes' or 'No') by two raters on initial (T S), end of treatment (T 0), and post-treatment (T 5) plaster models. A recession was noted (scored 'Yes') if the labial cemento-enamel junction was exposed. The clinical crown heights were measured at T S, T 0, and T 5 as the distances between the incisal edges and the deepest points of the curvature of the vestibulo-gingival margins. Determination of the facial type was based on the inclination of mandibular plane relative to cranial base (Sella-Nasion/Mandibular Plane) and the proportion of posterior to anterior face heights (PFHs; SGo/NMe × 100 per cent) on pre-treatment cephalograms. RESULTS: From T 0 to T 5, the number of subjects with recessions increased from 2 (1.1 per cent) to 24 (13.6 per cent), and the number of recession sites increased from 2 to 39. However, most patients had either one or two recession sites. The mean clinical crown height of mandibular incisors increased by 0.86mm (SD = 0.82, P < 0.001). Regression analysis showed that mandibular plane inclination had no effect on the development of gingival recession or on the increase of clinical crown heights of mandibular incisors. CONCLUSIONS: Facial type is not a predictor of the occurrence of gingival recession.

• MeSH
• dítě MeSH
• kefalometrie metody   MeSH
• kohortové studie MeSH
• lidé MeSH
• mandibula diagnostické zobrazování   patologie   MeSH
• mladiství MeSH
• následné studie MeSH
• obličejové kosti diagnostické zobrazování   patologie   MeSH
• ortodoncie korekční škodlivé účinky   metody   MeSH
• prognóza MeSH
• regresní analýza MeSH
• rentgendiagnostika zubní MeSH
• řezáky diagnostické zobrazování   patologie   MeSH
• rizikové faktory MeSH
• ústup dásní etiologie   patologie   MeSH
• zubní krček patologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). METHODS: Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1). RESULTS: Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples. CONCLUSIONS: The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology.

• MeSH
• akvaporin 4 krev   imunologie   MeSH
• autoprotilátky krev   imunologie   MeSH
• ELISA metody   MeSH
• imunohistochemie metody   MeSH
• lidé MeSH
• neuromyelitis optica krev   imunologie   MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 ± 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 ± 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 ± 5.1 years, SD) and later tetraplegia (mean age: 16.1 ± 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 ± 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 ± 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.

• MeSH
• adaptorový proteinový komplex 4 genetika   MeSH
• corpus callosum diagnostické zobrazování   MeSH
• dítě MeSH
• dospělí MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   trendy   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• průřezové studie MeSH
• registrace MeSH
• spastická paraplegie dědičná diagnostické zobrazování   genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

The bioavailability of memantine was compared using two tablet (Memantine LACHEMA 10 tbl. obd. and Akatinol® Memantine 10 tbl. obd., Study A) and two oral solution formulations (Memantine LACHEMA gtt. and Akatinol® Memantine gtt., Study B) containing 10 mg memantine hydrochloride in two randomized, two-period, two-sequence, crossover studies with 24 healthy volunteers. In both study periods, memantine concentrations were determined by gas-chromatography with electron-capture detection in plasma samples taken at the steady state after 22 days of once-daily dosing. The arithmetic mean (SD) pharmacokinetic parameters in the studies A and B were: AUC0-0t,ss 768 (141) vs. 727 (99) and 807 (154) vs. 836 (156) ng/ml h, Cmax,ss 37.3 (6.1) vs. 35.2 (4.5) and 39.2 (7.3) vs. 40.6 (6.7) ng/ml. Median values of Tmax were in the range of 4 to 5 h. Both tablet and oral solution formulations were found bioequivalent (90%-confidence intervals for AUC0-t,ss, Cmax,ss and Ct,ss within 101–114% (Study A) and 92 and 104% (Study B)). For the peak-trough fluctuation, the bioequivalence intervals were 85–107% and 86–04%, respectively. By pooled analysis of both studies, the geometric mean (90% CI) relative bioavailability of memantine from tablets compared to oral solutions was 91% (85–98).

• Klíčová slova
• Akatinol Memantine,
• MeSH
• Alzheimerova nemoc farmakoterapie   MeSH
• chromatografie plynová metody   využití   MeSH
• financování organizované MeSH
• interpretace statistických dat MeSH
• memantin aplikace a dávkování   farmakokinetika   MeSH

The intra- and extracerebral Doppler artery blood velocity responses to a 10-mmHg abrupt blood pressure (BP) decrease in ten healthy men were studied. This decrease was obtained using two cuffs placed over both thighs. First, cuffs were inflated to pressures greater than the arterial BP for 5 min. Next, they were deflated to 60 mmHg in order to prevent venous return from the legs. We obtained a decrease in mean arterial BP of from 101 (10) to 90 (10) mmHg [mean (SD), P < 0.01] without modifications in the heart rate [HR, 88 (14) beats min-1]. Middle cerebral artery mean blood velocity (MCAmv) decreased immediately from 50 (10) to 42 (12) cm s-1 (P < 0.05). Simultaneously, temporal superficial artery mean blood velocity (TSAmv) decreased from 11 (3) to 7 (2) cm s-1 (P < 0.05) and common carotid artery blood flow (CCAbf) decreased from 305 (23) to 233 (33) ml min-1 (P < 0.05). After 5 s, MCAmv and CCAbf returned to baseline values, whereas TSAmv [8 (2) cm s-1], mean arterial BP [86 (10) mmHg] remained low and HR increased [92 (12) beats min-1]. TSAmv, BP and HR returned to baseline values in 1 min. These data confirm that cerebral blood flow (CBF) is very rapidly regulated but that blood flow in extracranial territories is not and that it follows the arterial BP changes.

• MeSH
• arteriae carotides fyziologie   MeSH
• arteriae cerebrales * fyziologie   MeSH
• arteriae temporales fyziologie   MeSH
• dospělí MeSH
• konstrikce MeSH
• krevní tlak * fyziologie   MeSH
• lidé MeSH
• mozkový krevní oběh * fyziologie   MeSH
• rychlost toku krve * MeSH
• srdeční frekvence MeSH
• stehno krevní zásobení   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

PURPOSE: To evaluate the relationship between the ischemic index and the oxygen saturation in retinal vessels in patients with retinal vein occlusion. DESIGN: Prospective, cross-sectional study. METHODS: We performed a prospective study. The cohort consisted of 43 eyes of 43 patients with retinal vein occlusions (RVO), 23 of whom had central retinal vein occlusions (CRVO) and 20 who had branch retinal vein occlusions (BRVO). We evaluated the retinal vessel saturation using an automatic retinal oximetry device. The retinal ischemic index (ISI) was determined using ultra-widefield fluorescein angiography. RESULTS: Mean arterial saturation (±SD) was 100% ± 11%, mean vein saturation was 52% ±13%, and mean A-V difference was 48% ± 16% in eyes with BRVO. The average ISI in the same group was 0.48 (range 0-1). There was no statistically significant correlation between the retinal ischemic index and retinal saturation in the BRVO group. The affected eye in the CRVO group had a mean arterial saturation of 101% ± 6%, vein saturation of 44% ± 11 % and A-V difference of 58% ± 10%. The average ISI in the CRVO group was 0.54 (range 0-1). A statistically significant negative correlation between ISI and vein saturation was found in the CRVO group (r = -0.686; P =.0003). A significant positive correlation between ISI and the A-V difference was found in the CRVO group (r = 0.893; P <.0001). CONCLUSIONS: Oxygen saturation in the retinal vein and the arteriovenous difference correlated with the ischemic index in CRVO patients. No correlation was found for BRVO patients.

• MeSH
• fluoresceinová angiografie MeSH
• ischemie patofyziologie   MeSH
• kyslík krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• okluze retinální žíly patofyziologie   MeSH
• optická koherentní tomografie MeSH
• oxymetrie MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• senioři MeSH
• spotřeba kyslíku fyziologie   MeSH
• vena centralis retinae fyziologie   MeSH
• zraková ostrost MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

IMPORTANCE: Impaired exercise capacity is a cardinal manifestation of obstructive hypertrophic cardiomyopathy (HCM). The Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Obstructive HCM (SEQUOIA-HCM) is a pivotal study characterizing the treatment effect of aficamten, a next-in-class cardiac myosin inhibitor, on a comprehensive set of exercise performance and clinical measures. OBJECTIVE: To evaluate the effect of aficamten on exercise performance using cardiopulmonary exercise testing with a novel integrated measure of maximal and submaximal exercise performance and evaluate other exercise measures and clinical correlates. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified analysis from SEQUOIA-HCM, a double-blind, placebo-controlled, randomized clinical trial. Patients were recruited from 101 sites in 14 countries (North America, Europe, Israel, and China). Individuals with symptomatic obstructive HCM with objective exertional intolerance (peak oxygen uptake [pVO2] ≤90% predicted) were included in the analysis. Data were analyzed from January to March 2024. INTERVENTIONS: Randomized 1:1 to aficamten (5-20 mg daily) or matching placebo for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was change from baseline to week 24 in integrated exercise performance, defined as the 2-component z score of pVO2 and ventilatory efficiency throughout exercise (minute ventilation [VE]/carbon dioxide output [VCO2] slope). Response rates for achieving clinically meaningful thresholds for change in pVO2 and correlations with clinical measures of treatment effect (health status, echocardiographic/cardiac biomarkers) were also assessed. RESULTS: Among 282 randomized patients (mean [SD] age, 59.1 [12.9] years; 115 female [40.8%], 167 male [59.2%]), 263 (93.3%) had core laboratory-validated exercise testing at baseline and week 24. Integrated composite exercise performance improved in the aficamten group (mean [SD] z score, 0.17 [0.51]) from baseline to week 24, whereas the placebo group deteriorated (mean [SD] z score, -0.19 [0.45]), yielding a placebo-corrected improvement of 0.35 (95% CI, 0.25-0.46; P <.001). Further, aficamten treatment demonstrated significant improvements in total workload, circulatory power, exercise duration, heart rate reserve, peak heart rate, ventilatory efficiency, ventilatory power, and anaerobic threshold (all P <.001). In the aficamten group, large improvements (≥3.0 mL/kg per minute) in pVO2 were more common than large reductions (32% and 2%, respectively) compared with placebo (16% and 11%, respectively). Improvements in both components of the primary outcome, pVO2 and VE/VCO2 slope throughout exercise, were significantly correlated with improvements in symptom burden and hemodynamics (all P <.05). CONCLUSIONS AND RELEVANCE: This prespecified analysis of the SEQUOIA-HCM randomized clinical trial found that aficamten treatment improved a broad range of exercise performance measures. These findings offer valuable insight into the therapeutic effects of aficamten. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05186818.

• MeSH
• dvojitá slepá metoda MeSH
• hypertrofická kardiomyopatie * patofyziologie   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• spotřeba kyslíku fyziologie   MeSH
• srdeční myosiny MeSH
• tolerance zátěže * fyziologie   MeSH
• zátěžový test * metody   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

PURPOSE: Delayed achievement of target vancomycin serum concentrations may adversely affect clinical outcomes. The objective of this retrospective study was to explore the real frequency of loading dose use and to evaluate the impact of loading dose for the achievement of vancomycin PK/PD target in adult patients treated with intermittent vancomycin. As a secondary aim we determined optimal vancomycin loading dose based on individual pharmacokinetic calculations. METHODS: Vancomycin pharmacokinetic models were computed using two-compartmental analysis. Based on these models AUC24 were calculated. Unpaired t-test was used to compare AUC24 achieved in patients treated with and without vancomycin loading dose. RESULTS: Vancomycin loading dose was administered only in 17.8% patients. Volume of distribution and clearance median values (interquartile range) for vancomycin in whole study population (n = 45) were 0.69 (0.55-0.87) L/kg and 0.0304 (0.0217-0.0501) L/h/kg, respectively. The AUC24 was significantly higher in patients taking loading dose compared with the group without loading dose: mean (SD) AUC24 was 496 (101) vs. 341 (77) mg h/L. Proportion of patients reaching PK/PD goal was 87.5% and 24.3% with and without loading dose administration, respectively. Considering individual pharmacokinetic parameters optimal vancomycin loading dose was 27.5 mg/kg of body weight. CONCLUSIONS: Loading dose administration plays crucial part in rapid attainment of vancomycin PK/PD target in adult patient treated with intermittent vancomycin, although it is not frequently used in clinical practise. The optimal loading dose of 25-30 mg/kg of body weight should be routinely administered to adult patients treated with intermittent vancomycin.

• MeSH
• antibakteriální látky aplikace a dávkování   krev   farmakokinetika   farmakologie   MeSH
• infuzní pumpy MeSH
• kreatinin krev   MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• plocha pod křivkou MeSH
• počítačová simulace MeSH
• retrospektivní studie MeSH
• senioři MeSH
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