PURPOSE: A healthy lifestyle may prevent or mitigate late effects in childhood, adolescent and young adult (CAYA) cancer survivors. To support survivors in adopting healthier behaviours, the PanCareFollowUp (PCFU) Lifestyle intervention was developed, encompassing 4 months of online lifestyle coaching aimed at achieving a personal lifestyle goal. The aims of this study were to (1) determine the efficacy of this intervention on lifestyle outcomes over time and (2) identify predictors for goal achievement. PATIENTS AND METHODS: Fifty-eight survivors were enrolled. Outcomes were assessed at baseline (T0), after 4 months of coaching (T1) and after 4 months of follow-up (T2). The primary outcome included the percentage of survivors successful in achieving and sustaining their goal, whereas secondary outcomes included differences in body mass index (BMI), diet and physical activity. To evaluate the adjusted, longitudinal effects on secondary outcomes, linear mixed models were estimated. Predictors for goal achievement were identified through logistic regression analysis. RESULTS: At T1 and T2, 68% and 76% of goals were achieved or sustained, respectively. Mean differences between T2 and T0 showed significant improvements in BMI (-0.5 kg/m2), diet (-0.6 points) and physical activity (+7.7 h/week). Estimation of multivariable models also showed positive effects. Participants with a lower BMI and fewer depressive feelings at baseline were more likely to achieve and/or sustain their goals at T2. CONCLUSION: Findings suggest that the PCFU Lifestyle intervention supports survivors in making lifestyle changes. Results can be used to inform a subsequent randomised intervention study and integrate lifestyle coaching into care. TRIAL REGISTRATION: International Clinical Trial Registry Platform (ICTRP) number: NL8932 (ICTRP Search Portal [who. int]). Registered on 29 September 2020.
- MeSH
- cvičení * MeSH
- dítě MeSH
- dospělí MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory terapie psychologie MeSH
- přežívající onkologičtí pacienti * psychologie MeSH
- telemedicína * MeSH
- zdravý životní styl MeSH
- životní styl MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: New generation androgen receptor-targeting agents (ARTA) have been in the spotlight for their efficacy in metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific antigen (PSA) represents one of the most commonly used serum cancer biomarkers worldwide. The present retrospective study focused on the prognostic role of serum PSA isoforms and their early dynamics in mCRPC patients treated with abiraterone acetate (ABI) or enzalutamide (ENZ). PATIENTS AND METHODS: The association between outcomes of 334 mCRPC patients treated with ABI or ENZ and the levels of serum total PSA (tPSA), free PSA (fPSA), [-2]proPSA and the Prostate Health Index (PHI) at baseline and one month after treatment initiation was analyzed retrospectively. RESULTS: In the multivariable Cox proportional hazards models, baseline tPSA>50 μg/l (p<0.001), and [-2]proPSA>300 ng/l (p=0.017) remained independent significant factors associated with inferior OS, while baseline fPSA>1.75 μg/l (p=0.050) and Δ [-2]proPSA >-50% approached statistical significance (p=0.062). The results of ROC analyses assessing the ability of baseline tPSA, fPSA, and [-2]proPSA to predict mortality within two years showed area under the curve (AUC) values of 0.709, 0.685, and 0.740, respectively. Among the subgroup with baseline tPSA≤20.0 μg/l, the results of ROC analyses for baseline tPSA, fPSA and [-2]proPSA showed AUC values of 0.441, 0.682, and 0.688, respectively. CONCLUSION: Our results suggest a significant correlation between pretreatment serum levels of tPSA and [-2]proPSA with OS in mCRPC patients receiving ARTA.
- MeSH
- abirateron terapeutické užití aplikace a dávkování MeSH
- androgenní receptory * krev metabolismus MeSH
- antagonisté androgenních receptorů terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádorové biomarkery krev MeSH
- nádory prostaty rezistentní na kastraci * farmakoterapie krev patologie mortalita MeSH
- prognóza MeSH
- prostatický specifický antigen * krev MeSH
- protein - isoformy * krev MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Through the agnostic screening of patients with uncharacterised disease phenotypes for an upregulation of type I interferon (IFN) signalling, we identified a cohort of individuals heterozygous for mutations in PTPN1, encoding the protein-tyrosine phosphatase 1B (PTP1B). We aimed to describe the clinical phenotype and molecular and cellular pathology of this new disease. METHODS: In this case series, we identified patients and collected clinical and neuroradiological data through collaboration with paediatric neurology and clinical genetics colleagues across Europe (Czechia, France, Germany, Italy, Slovenia, and the UK) and Israel. Variants in PTPN1 were identified by exome and directed Sanger sequencing. The expression of IFN-stimulated genes was determined by quantitative (q) PCR or NanoString technology. Experiments to assess RNA and protein expression and to investigate type 1 IFN signalling were undertaken in patient fibroblasts, hTERT-immortalised BJ-5ta fibroblasts, and RPE-1 cells using CRISPR-Cas9 editing and standard cell biology techniques. FINDINGS: Between Dec 20, 2013, and Jan 11, 2023, we identified 12 patients from 11 families who were heterozygous for mutations in PTPN1. We found ten novel or very rare variants in PTPN1 (frequency on gnomAD version 4.1.0 of <1·25 × 10:sup>-6). Six variants were predicted as STOP mutations, two involved canonical splice-site nucleotides, and two were missense substitutions. In three patients, the variant occurred de novo, whereas in nine affected individuals, the variant was inherited from an asymptomatic parent. The clinical phenotype was characterised by the subacute onset (age range 1-8 years) of loss of motor and language skills in the absence of seizures after initially normal development, leading to spastic dystonia and bulbar involvement. Neuroimaging variably demonstrated cerebral atrophy (sometimes unilateral initially) or high T2 white matter signal. Neopterin in CSF was elevated in all ten patients who were tested, and all probands demonstrated an upregulation of IFN-stimulated genes in whole blood. Although clinical stabilisation and neuroradiological improvement was seen in both treated and untreated patients, in six of eight treated patients, high-dose corticosteroids were judged clinically to result in an improvement in neurological status. Of the four asymptomatic parents tested, IFN signalling in blood was normal (three patients) or minimally elevated (one patient). Analysis of patient blood and fibroblasts showed that tested PTPN1 variants led to reduced levels of PTPN1 mRNA and PTP1B protein, and in-vitro assays demonstrated that loss of PTP1B function was associated with impaired negative regulation of type 1 IFN signalling. INTERPRETATION: PTPN1 haploinsufficiency causes a type 1 IFN-driven autoinflammatory encephalopathy. Notably, some patients demonstrated stabilisation, and even recovery, of neurological function in the absence of treatment, whereas in others, the disease appeared to be responsive to immune suppression. Prospective studies are needed to investigate the safety and efficacy of specific immune suppression approaches in this disease population. FUNDING: The UK Medical Research Council, the European Research Council, and the Agence Nationale de la Recherche.
- MeSH
- dítě MeSH
- haploinsuficience * genetika MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mutace genetika MeSH
- nemoci mozku genetika MeSH
- neurozánětlivé nemoci genetika MeSH
- předškolní dítě MeSH
- tyrosinfosfatasa nereceptorového typu 1 * genetika MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: This case series evaluated the clinical efficacy of the novel "lateral approach" combined with an enamel matrix derivative (EMD) and bone grafting in the regenerative surgical treatment of intrabony defects associated with an edentulous ridge. MATERIAL AND METHODS: The innovative flap, called the "lateral approach," is explicitly designed for regeneration of unchallenged isolated intrabony defects associated with edentulous alveolar ridges. The flap is defined by a curved vertical incision on the buccal side opposite the treated defect and a sulcular incision on the buccal and defect-associated sides, promoting uneventful healing and regeneration while minimizing complications. Seven intrabony defects (one per patient) distal to the lower second molar were treated using the "lateral approach" combined with EMD and grafting with deproteinized bovine bone mineral. The primary outcome was clinical attachment level (CAL) change. As additional parameters, pocket probing depth (PPD) reduction and complication rate were analyzed. All the outcomes were assessed 6 months post-surgery and compared with the baseline values. RESULTS: Primary wound healing occurred in 100% of cases, and no complications were reported. At the 6-month re-evaluation, the initial median CAL of 6 mm (interquartile range 5-8 mm) was reduced to 3 mm (3-5 mm). The corresponding median PPD was reduced from 6 mm (IQR 6-8 mm) to 4 mm (IQR 3-5 mm). These differences were statistically significant (p < 0.05). CONCLUSIONS: The "lateral approach" is a technique for the surgical treatment of intrabony defects associated with the edentulous ridge. Within the limitations of the study, this method seems to be suitable for distal intrabony defects in the lower second molars, which frequently develop after third molar extraction.
- MeSH
- augmentace alveolárního výběžku * metody MeSH
- čelist bezzubá chirurgie MeSH
- chirurgické laloky transplantace MeSH
- dospělí MeSH
- hojení ran MeSH
- kostní náhrady terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- proteiny zubní skloviny terapeutické užití MeSH
- regenerace kostí MeSH
- resorpce alveolární kosti * chirurgie MeSH
- řízená tkáňová regenerace parodontu metody MeSH
- senioři MeSH
- transplantace kostí metody MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Randomized clinical trials demonstrated similar efficacy and improved safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation (AF). Long-term data in routine clinical practice are needed. HYPOTHESIS: Patients with AF receiving edoxaban at baseline continue to have low annualized effectiveness and safety event rates in the second year of follow-up, with regional variations observed. METHODS: The Global ETNA-AF program is a prospective, noninterventional study of patients with AF receiving edoxaban. Patient characteristics and annualized clinical event rates were assessed overall and by region across the 2-year follow-up. Annualized event rates of bleeding and thromboembolic events were assessed within the first year and conditionally in patients who were event-free up to 12 months in the second year. RESULTS: This analysis comprised 26 805 patients from Europe (n = 13 164), Japan (n = 10 342), and non-Japanese Asian regions (n = 3299). Patients from Europe had the highest burden of comorbidities. The annualized event rates for major bleeding, any stroke, all-cause death, and cardiovascular death varied by region. The global annualized event rates in the first and second year were 1.31%/year and 0.86%/year for major bleeding, 1.06%/year and 0.65%/year for any stroke, 0.84%/year and 0.73%/year for cardiovascular death, and 3.05%/year and 3.18%/year for all-cause death. CONCLUSION: Annualized event rates for any stroke and major bleeding remained low through 2-year follow-up for patients with AF receiving edoxaban at baseline. Differences in annualized event rates for all-cause and cardiovascular mortality between Europe, Japan, and non-Japanese Asian regions may reflect variations in baseline characteristics. TRIAL REGISTRATION: Europe, NCT02944019; Japan, UMIN000017011; Korea/Taiwan, NCT02951039; Hong Kong, NCT03247582; and Thailand, NCT03247569.
- MeSH
- časové faktory MeSH
- cévní mozková příhoda prevence a kontrola epidemiologie etiologie MeSH
- fibrilace síní * farmakoterapie komplikace MeSH
- incidence MeSH
- inhibitory faktoru Xa * terapeutické užití škodlivé účinky MeSH
- krvácení * chemicky indukované epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- prospektivní studie MeSH
- pyridiny * terapeutické užití škodlivé účinky MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- thiazoly * terapeutické užití škodlivé účinky MeSH
- tromboembolie prevence a kontrola epidemiologie etiologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
OBJECTIVE: This study aimed to compare the force degradation of intermaxillary elastics (IE) in vitro and in vivo while stretching the IE to a precise diameter. MATERIALS AND METHODS: IE 3/16′′ medium Dentaurum from five different batches of packaging were analyzed. The in vivo study involved 10 volunteers, of which 100 IE were examined. To achieve three times the original diameter of the elastic, the distance between the upper canine and the lower dental arch was measured. Buttons were then placed in the mouth accordingly, and IE and passive aligners were inserted for five sessions of 48 h each. To investigate in vitro, 100 IE were placed in an incubator set at 37°C in a humid environment and stretched three times their diameter. The force of the elastics was measured in both investigations using a force meter at 0, 2, 8, 24, and 48 h. RESULTS: In all patients except one, the three times diameter distance extended from the upper canine to the lower second premolar. The force degradation in vivo at 2, 8, 24, and 48 h was 20.58%, 26.78%, 34.81%, and 38.56% and in vitro was 16.38%, 22.83%, 28.32%, and 30.78%. CONCLUSIONS: The amount of stretching of IE varies for each patient when using standard insertion points. The force of IE decreases exponentially, the force degradation in vivo being higher. The clinician must consider the force decrease when advising the patient of the time interval to change the elastics.
- MeSH
- analýza zatížení zubů MeSH
- dospělí MeSH
- latex * chemie MeSH
- lidé MeSH
- mechanický stres MeSH
- mladý dospělý MeSH
- ortodontické aparáty MeSH
- ortodontické přístroje - design MeSH
- testování materiálů * MeSH
- zubní oblouk MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND: Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study. METHODS: Vivacity-MG3 was a phase 3, randomised, double-blind, placebo-controlled, phase 3 study conducted at 81 outpatient centres with expertise in myasthenia gravis in 17 countries in Asia-Pacific, Europe, and North America. Adults (aged ≥18 years) with generalised myasthenia gravis inadequately controlled with standard-of-care therapy (MG-ADL score ≥6) were randomly assigned (1:1) to either nipocalimab (30 mg/kg loading dose then 15 mg/kg every 2 weeks for maintenance dosing) or placebo infusions every 2 weeks, added to standard-of-care therapy in both groups, for 24 weeks. Randomisation was stratified by antibody status, day 1 MG-ADL total score, and region. The sponsor, investigators, clinical raters, and participants were masked to treatment assignment. The primary endpoint was the difference between nipocalimab and placebo based on least-squares mean change from baseline in MG-ADL total score averaged over weeks 22, 23, and 24 in the intention-to-treat population of patients who were antibody-positive (for AChR, anti-muscle-specific tyrosine kinase [MuSK], or anti-low-density lipoprotein receptor-related protein 4 [LRP4]). Adverse events were assessed in patients who received at least one dose of study drug. This study is registered at ClinicalTrials.gov, NCT04951622; the double-blind phase is completed and an open-label extension phase is ongoing. FINDINGS: Between July 15, 2021, and Nov 17, 2023, 199 patients were enrolled, and 196 patients received study drug (98 in the nipocalimab group and 98 in the placebo group); of these, 153 (77 in the nipocalimab group and 76 in the placebo group) were antibody-positive. The least-squares mean change in MG-ADL score from baseline to weeks 22, 23, and 24 was -4·70 (SE 0·329) in the nipocalimab group versus -3·25 (0·335) in the placebo group (difference -1·45 [95% CI -2·38 to -0·52]; p=0·0024). The incidence of adverse events was similar between groups (82 [84%] of 98 in both the nipocalimab and placebo groups), including infections (42 [43%] of 98 in the nipocalimab group and placebo group) and headache (14 [14%] of 98 in the nipocalimab group and 17 [17%] of 98 in the placebo group). Serious adverse events were reported for nine (9%) of 98 patients in the nipocalimab group and 14 (14%) of 98 patients in the placebo group, three of which had a fatal outcome (nipocalimab: myasthenic crisis; placebo: cardiac arrest and myocardial infarction). INTERPRETATION: Results from the completed double-blind phase of Vivacity-MG3 support the role of nipocalimab, added to standard-of-care therapies, as a safe treatment for sustained disease control over 6 months for a broad population of patients with generalised myasthenia gravis who are antibody-positive. The ongoing open-label extension phase should provide longer term sustained safety and efficacy data with nipocalimab. FUNDING: Janssen Research & Development, LLC, a Johnson & Johnson company.
- MeSH
- činnosti denního života MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- myasthenia gravis * farmakoterapie MeSH
- receptory cholinergní imunologie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- 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
Current diagnostic methods for dyslexia primarily rely on traditional paper-and-pencil tasks. Advanced technological approaches, including eye-tracking and artificial intelligence (AI), offer enhanced diagnostic capabilities. In this paper, we bridge the gap between scientific and diagnostic concepts by proposing a novel dyslexia detection method, called INSIGHT, which combines a visualisation phase and a neural network-based classification phase. The first phase involves transforming eye-tracking fixation data into 2D visualisations called Fix-images, which clearly depict reading difficulties. The second phase utilises the ResNet18 convolutional neural network for classifying these images. The INSIGHT method was tested on 35 child participants (13 dyslexic and 22 control readers) using three text-reading tasks, achieving a highest accuracy of 86.65%. Additionally, we cross-tested the method on an independent dataset of Danish readers, confirming the robustness and generalizability of our approach with a notable accuracy of 86.11%. This innovative approach not only provides detailed insight into eye movement patterns when reading but also offers a robust framework for the early and accurate diagnosis of dyslexia, supporting the potential for more personalised and effective interventions.
- MeSH
- čtení MeSH
- dítě MeSH
- dyslexie * patofyziologie diagnóza klasifikace MeSH
- lidé MeSH
- neuronové sítě * MeSH
- oční fixace * fyziologie MeSH
- pohyby očí fyziologie MeSH
- technologie sledování pohybu očí * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The eye represents a highly specialized organ, with its main function being to convert light signals into electrical impulses. Any damage or disease of the eye induces a local inflammatory reaction that could be harmful for the specialized ocular cells. Therefore, the eye developed several immunoregulatory mechanisms which protect the ocular structures against deleterious immune reactions. This protection is ensured by the production of a variety of immunosuppressive molecules, which create the immune privilege of the eye. In addition, ocular cells are potent producers of numerous growth and trophic factors which support the survival and regeneration of diseased and damaged cells. If the immune privilege of the eye is interrupted and the regulatory mechanisms are not sufficiently effective, the eye disease can progress and result in worsening of vision or even blindness. In such cases, external immunotherapeutic interventions are needed. One perspective possibility of treatment is represented by mesenchymal stromal/stem cell (MSC) therapy. MSCs, which can be administered intraocularly or locally into diseased site, are potent producers of various immunoregulatory and regenerative molecules. The main advantages of MSC therapy include the safety of the treatment, the possibility to use autologous (patient's own) cells, and observations that the therapeutic properties of MSCs can be intentionally regulated by external factors during their preparation. In this review, we provide a survey of the immunoregulatory and regenerative mechanisms in the eye and describe the therapeutic potential of MSC application for corneal damages and retinal diseases.
BACKGROUND: Extensive surgical resection of the thoracic aorta in patients with type A aortic dissection (TAAD) is thought to reduce the risk of late aortic wall degeneration and the need for repeat aortic operations. OBJECTIVES: We evaluated the early and late outcomes after aortic root replacement and supracoronary ascending aortic replacement in patients with TAAD involving the aortic root. DESIGN: Retrospective, multicenter cohort study. METHODS: The outcomes after aortic root replacement and supracoronary ascending aortic replacement in patients with TAAD involving the aortic root, that is dissection flap located at least in one of the Valsava segments, were herein evaluated. In-hospital mortality, neurological complications, dialysis as well as 10-year repeat proximal aortic operation, and mortality were the outcomes of this study. RESULTS: Supracoronary ascending aortic replacement was performed in 198 patients and aortic root replacement in 215 patients. During a mean follow-up of 4.0 ± 4.0 years, 19 patients underwent 22 repeat procedures on the aortic root and/or aortic valve. No operative death occurred after these reinterventions. The risk of proximal aortic reoperation was significantly lower in patients who underwent aortic root replacement (5.5% vs 12.9%, adjusted subdistributional hazard ratio (SHR) 0.085, 95% CI 0.022-0.329). Aortic root replacement was associated with higher rates of in-hospital (14.4% vs 12.1%, adjusted odds ratio 2.192, 95% CI 1.000-4.807) and 10-year mortality (44.5% vs 30.4%, adjusted hazard ratio 2.216, 95% CI 1.338-3.671). Postoperative neurological complications and dialysis rates were comparable in the study groups. CONCLUSION: Among patients with TAAD involving the aortic root, its replacement was associated with a significantly lower rate of repeat proximal aortic operation of any type compared to supracoronary aortic replacement. Still, aortic root replacement seems to be associated with an increased risk of mortality in these patients. UNLABELLED: ClinicalTrials.gov: NCT04831073 (https://clinicaltrials.gov/study/NCT04831073).
- MeSH
- aneurysma hrudní aorty * chirurgie mortalita diagnostické zobrazování MeSH
- časové faktory MeSH
- cévy - implantace protéz * škodlivé účinky mortalita MeSH
- disekce aorty * chirurgie mortalita MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- lidé středního věku MeSH
- lidé MeSH
- mortalita v nemocnicích * MeSH
- pooperační komplikace * epidemiologie etiologie mortalita MeSH
- reoperace MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- srovnávací studie MeSH