BACKGROUND: Diabetes mellitus (DM) is a chronic disease with prevalence increasing worldwide. The aim of this study was to investigate satisfaction with the current method of insulin delivery (INS) amongst patient with type 1 diabetes mellitus (T1DM) using multiple daily injection (MDI) or continuous subcutaneous insulin infusion (CSII). Furthermore, a sub-aim was to test the effect of selected variables on patient satisfaction with MDI or CSII using regression analysis. METHODS: A cross-sectional study carried out in the territory of Moravia in the Czech Republic. A quantitative approach using the Insulin Delivery System Rating Questionnaire (IDSRQ) among 197 respondents with T1DM with INS delivery with MDI or CSII for at least 1 year. Statistical methods used were descriptive statistics, Student's t-tests and regression analysis. RESULTS: Highly significant differences were found between CSII and MDI patients in satisfaction with the current method of INS delivery (p < 0.001), in how the current method of delivery helps patients maintain stable blood glucose values, prevent high blood glucose (p < 0.001), and in overall satisfaction with the current method of INS delivery (p < 0.001). The average overall satisfaction score was 56.19 points for MDI and 62.08 points for CSII. Regression analysis revealed predictors of overall satisfaction on the mean score on how the current method of INS delivery helps MDI patients (p < 0.01). The effect of other selected variables was not confirmed. CONCLUSION: The results of the study showed higher overall satisfaction with the method of INS delivery in CSII patients. The current method of INS delivery does not interfere with daily life and activities in most patients.

• MeSH
• diabetes mellitus 1. typu * farmakoterapie   krev   psychologie   MeSH
• dospělí MeSH
• hypoglykemika * aplikace a dávkování   terapeutické užití   MeSH
• injekce subkutánní MeSH
• inzulin * aplikace a dávkování   terapeutické užití   MeSH
• inzulinové infuzní systémy * MeSH
• krevní glukóza MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• spokojenost pacientů * MeSH
• subkutánní infuze MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Intravenous immunoglobulins (IVIG) are commonly used in peri-transplant desensitization, but evidence supporting their efficacy is limited. We conducted a prospective, randomized single-center, open-label, Phase IIIb non-inferiority clinical pilot trial to compare the efficacy of IVIG (administered at a dose of 3 × 0.5 g/kg) versus no IVIG, in conjunction with rabbit anti-thymocyte globulin (5-7 mg/kg) induction, in pre-sensitized patients with donor-specific antibodies who had negative pre-transplantation Flow- and CDC-crossmatches, between July 2020 and November 2022. The primary endpoint was the rate of efficacy failure, defined as biopsy-proven rejection within 12-month post-transplant. Secondary endpoints included the incidence of rejection at protocol biopsies, evaluated by histology and biopsy-based transcripts diagnostics. Of the screened patients, 53 (72.6%) were excluded due to crossmatch positivity. Ten patients were randomized to the IVIG+, and 7 to the IVIG-arm. The trial was prematurely terminated due to futility at interim analysis. In the IVIG-arm, 3 patients (43%) experienced the primary endpoint compared to none in the IVIG+ arm (p = 0.026). MMDx identified one molecular ABMR in the IVIG+ and 2 in the IVIG-arm in 12-month protocol biopsies. There was one graft loss in the IVIG-arm. The results of this pilot study, although not definitive, do not support the use of IVIG-sparing regimens in HLA-incompatible kidney transplantation (NCT04302805). This study is registered on ClinicalTrials.gov under the identifier NCT04302805.

• MeSH
• antilymfocytární sérum * aplikace a dávkování   MeSH
• desenzibilizace imunologická * metody   MeSH
• dospělí MeSH
• intravenózní imunoglobuliny * aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• rejekce štěpu * prevence a kontrola   imunologie   MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH

Inflammatory lung diseases (ILDs) represent a global public health crisis characterized by escalating prevalence, significant morbidity, and substantial mortality. In response to the complex immunopathogenic mechanisms driving these conditions, novel pharmacological strategies targeting resolution pathways have emerged throughout the discovery of specialized pro-resolving lipid mediator (SPM; resolvins, maresins, and protectins) dysregulation across the ILD spectra, positioning these endogenous molecules as promising therapeutic candidates for modulating maladaptive inflammation and promoting tissue repair. Over the past decade, this paradigm has catalyzed extensive translational research into SPM-based interventions as precision therapeutics for respiratory inflammation. In asthma, they reduce mucus hypersecretion, bronchial hyperreactivity, and airway inflammation, with prenatal SPM exposure potentially lowering offspring disease risk. In COPD, SPMs attenuate amyloid A-driven inflammation, normalizing cytokine/chemokine imbalances and oxidative stress and mitigating COVID-19-associated cytokine storm, enhancing survival. This review synthesizes SPMs' pharmacotherapeutic mechanisms in ILDs and evaluates current preclinical and clinical evidence.

• MeSH
• chronická obstrukční plicní nemoc farmakoterapie   metabolismus   MeSH
• COVID-19 metabolismus   MeSH
• kyseliny dokosahexaenové terapeutické užití   metabolismus   MeSH
• lidé MeSH
• plicní nemoci * farmakoterapie   metabolismus   MeSH
• SARS-CoV-2 MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: The objective of this systematic review is to evaluate the efficacy and safety of antigen-specific tolerance-inducing therapeutic approaches (products based on peptides, DNA and T cells) versus placebo or other comparators, where possible, in adult multiple sclerosis (MS) patients. METHODS: PubMed, CINAHL, Web of Science, Cochrane and International Clinical Trials Registry Platform, ClinicalTrials.gov were searched for published and unpublished studies. Screening, critical appraisal, and data extraction for included studies were carried out by two independent reviewers. For efficacy, phase I, II and III clinical trials (randomized/non-randomized; double blind/single blind/unblinded; single-center/multicenter; single-arm/two-arm) and for safety, phase I, II and III clinical trials (randomized/non-randomized; double blind/single blind/unblinded; controlled/uncontrolled; single-center/multicenter; single-arm/two-arm) were included. Observational studies (cross-sectional studies, cohort studies, case studies/reports etc), review articles, systematic reviews, meta-analysis, preclinical and pilot studies were excluded. All included studies were critically appraised using standardized JBI tools, with no exclusions based on methodological quality. Where possible, studies were pooled in statistical meta-analysis, presented in tabular format, and accompanied by narrative synthesis. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for grading the certainty of evidence. RESULTS: Search yielded 2644 results and in total 26 studies were included in the final analysis. Twelve studies were RCTs and 14 were quasi-experimental. In total, there were 1427 subjects from the RCTs, and 314 from non-RCTs. Sample size of studies ranged from 10 to 612 patients. All studies included adult patients, principally aged 18-55/65 years. Critical appraisal scores for the RCTs were in the range 31% to 92%. For quasi-experimental studies, critical appraisal scores were in the range 45% to 78%. Due to high heterogeneity of the studies, efficacy of all antigen-specific treatment remained ambiguous. For all three types of treatment, there was no statistical difference in occurrence of adverse effects (AEs) between the treatment- and placebo-related AEs (for DNA-based treatment RR was 1.06 (0.94-1.10), p = 0.334; for peptides-base treatments RR was 1.04 (0.90-1.08), p = 0.115; for T-cells-based treatments RR was 1.31 (0.97-1.76), p = 0.08). There were no differences in RR for serious AEs (SAEs) between the treatments either for DNA-based treatment (RR was 0.63 (0.25-1.58), p = 0.322) or peptide-based treatment (RR was 0.86 (0.62-1.19), p = 0.361). There were no reported SAEs for T cell-based treatments, so meta-analysis for these therapies was not performed. The most frequent AEs were local reactions to injection, such as redness, erythema, pain. DISCUSSION: Antigen-specific tolerance-inducing therapeutic approaches appeared to be safe. However, the certainty for these results was very low for SAEs in peptide- and DNA-based therapies, whereas it was low for AEs in DNA- and T cells-based therapies and moderate for AEs in peptide-based therapies. The efficacy of antigen-specific therapies remains ambiguous. Larger, well-designed studies with high level quality are needed to ensure ultimate conclusions. REGISTRATION: The registration number provided following registration of the protocol in PROSPERO is 'CRD42021236776'.

• MeSH
• antigeny * imunologie   terapeutické užití   MeSH
• lidé MeSH
• roztroušená skleróza * terapie   imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH

CONTEXT: SB16 is a proposed biosimilar to reference denosumab (DEN; brand name: Prolia). OBJECTIVE: This phase 3 randomized, double-blind, multicenter study evaluated the biosimilarity of SB16 to DEN in women with postmenopausal osteoporosis (NCT04664959). DESIGN: The study included 457 postmenopausal osteoporosis patients who had a lumbar spine or total hip T-score between -2.5 and -4. Patients were randomized in a 1:1 ratio to receive either 60 mg of SB16 or DEN subcutaneously at month 0 and month 6. At month 12, patients were rerandomized to continue with the assigned treatment or switch from DEN to SB16 up to month 18. This report includes results up to month 12. METHODS: The primary endpoint was the percent change from baseline in lumbar spine bone mineral density (BMD) at month 12. Secondary endpoints including the percent change from baseline in BMD of the lumbar spine (except for month 12), total hip, and femoral neck; pharmacokinetic, pharmacodynamic (serum C-telopeptide of type I collagen, and procollagen type I N-terminal propeptide), safety, and immunogenicity profiles were measured up to month 12. RESULTS: The least-squares mean differences in percent change from baseline in lumbar spine BMD at month 12 were 0.33% (90% CI, -0.25 to 0.91) in the full analysis set and 0.39% (95% CI, -0.36 to 1.13) in the per-protocol set; both within the predefined equivalence margin. The secondary endpoints were comparable between the 2 treatment groups. CONCLUSION: The reported efficacy, pharmacokinetic, pharmacodynamic, safety, and immunogenicity data support the biosimilarity of SB16 to DEN.

• MeSH
• bederní obratle účinky léků   diagnostické zobrazování   MeSH
• biosimilární léčivé přípravky * terapeutické užití   farmakokinetika   aplikace a dávkování   škodlivé účinky   MeSH
• denosumab * terapeutické užití   farmakokinetika   škodlivé účinky   aplikace a dávkování   MeSH
• dvojitá slepá metoda MeSH
• inhibitory kostní resorpce * terapeutické užití   farmakokinetika   aplikace a dávkování   škodlivé účinky   MeSH
• kostní denzita účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• postmenopauzální osteoporóza * farmakoterapie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Publikace se zaměřuje na radiační onkologii a na možnosti radioterapie nádorových nemocí. Určeno odborné veřejnosti.

• MeSH
• nádory radioterapie   MeSH
• radiační onkologie MeSH
• radioterapie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• onkologie
• radiologie, nukleární medicína a zobrazovací metody
• NLK Publikační typ
• kolektivní monografie

Identifying biological markers to guide treatment decisions in first-episode psychosis (FEP) is essential for improving patient outcomes. This longitudinal study investigated DNA methylation (DNAm) patterns and DNAm-derived cell-type proportions (CTP) in blood and associated them with response to risperidone treatment, a second-generation antipsychotic drug, in antipsychotic-naïve FEP patients. We also explored longitudinal changes in DNAm associated with risperidone treatment. We profiled DNAm in 114 individuals before (anFEP) and after two months of risperidone treatment using microarrays. The main results were compared with 115 healthy controls and validated in an independent cohort of subjects with schizophrenia (n = 26) with one-month follow-up data. We identified 302 differentially methylated positions (DMPs) associated with treatment response, measured by changes in the Positive and Negative Syndrome Scale score, of which 16 were validated in the independent cohort. Sixteen differentially methylated regions (DMRs) were associated with response, with one (in SIPA1L3) being validated. A decrease in B-cell proportions was correlated with symptom improvement in both cohorts. Additionally, four DMPs associated with risperidone treatment were identified: two related to the psychotic state and two specifically to risperidone treatment. DNAm-derived CTP showed alterations in anFEP compared with controls, particularly in the neutrophil-to-lymphocyte ratio, which normalized after treatment. These findings suggest that DNAm, particularly in B-cells, may be a promising marker for monitoring response to risperidone treatment in schizophrenia. Our longitudinal study revealed novel and known genes that may be regulated by risperidone and could be used as response markers to improve prognosis in schizophrenia and FEP.

• MeSH
• antipsychotika * terapeutické užití   MeSH
• dospělí MeSH
• lidé MeSH
• longitudinální studie MeSH
• metylace DNA * účinky léků   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• psychotické poruchy * farmakoterapie   genetika   krev   MeSH
• risperidon * terapeutické užití   farmakologie   MeSH
• schizofrenie * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Epilepsy in children is often associated with impaired quality of life, lower academic achievement, and reduced academic self-concept, as well as an increased risk of depression and anxiety. This study aims to evaluate the possible impact of comorbidities, such as learning disabilities (LD) and attention deficit hyperactivity disorder (ADHD), on these variables. METHODS: A total of 104 children with epilepsy (CWE) aged 8-15 years, attending mainstream schools, participated in the study. Of these, 45 were diagnosed with LD and/or ADHD. Participants completed the CHEQOL-25 questionnaire to assess quality of life (QoL), the SPAS questionnaire to evaluate academic self-concept, as well as inventories measuring depressive and anxiety symptoms. The data were analyzed to identify differences between subgroups with and without LD/ADHD using a two-sample t-test. Additionally, correlation analysis was conducted to identify other relevant variables influencing QoL, academic self-concept, and depressive and anxiety symptoms. RESULTS: QoL and academic self-concept were significantly poorer in CWE with LD/ADHD compared to those without comorbidities. QoL showed statistically significant associations with depressive and anxiety symptoms, and academic self-concept. While depressive symptoms levels in CWE without comorbidities align with those in the general population, CWE with LD/ADHD showed an increased association with depressive symptoms. Although anxiety symptoms were relatively strongly associated with depressive symptoms, their prevalence remains broadly comparable to that of children without epilepsy, regardless of the presence of LD/ADHD. CONCLUSION: CWE with LD/ADHD and their families may benefit from focused attention, including targeted counseling and therapeutic interventions. However, specific interventional studies are recommended, based on child-specific findings.

• MeSH
• deprese epidemiologie   psychologie   MeSH
• dítě MeSH
• duševní zdraví * MeSH
• epilepsie * psychologie   epidemiologie   komplikace   MeSH
• hyperkinetická porucha epidemiologie   psychologie   MeSH
• komorbidita MeSH
• kvalita života * psychologie   MeSH
• lidé MeSH
• mladiství MeSH
• poruchy učení * epidemiologie   psychologie   MeSH
• průzkumy a dotazníky MeSH
• sebepojetí * MeSH
• úzkost epidemiologie   psychologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Arrested or protracted labor in nulliparous women caused by insufficient uterine contractility is a common problem in obstetrics, for which few management guidelines exist. The European Association of Perinatal Medicine nominated an expert panel, consisting of specialists in obstetrics and gynecology and midwives representing their respective professional national societies in nine European countries and patient representatives. The panel developed an evidence-based guideline for clinical practice supported by the Knowledge Institute of the Dutch Association of Medical Specialists. Five priority clinical questions (PICOs) were identified on nulliparous women, at term, with a singleton fetus, in cephalic presentation, and the diagnosis of arrested or protracted labor. For each question relevant outcome measures were defined as well as a minimal clinically important difference for each of them. Five literature searches were performed by an information specialist and articles were selected independently by two panel members. The GRADE methodology was used to write evidence summaries, considerations, and recommendations. The draft guideline was sent out for review to scientific societies involved in perinatal care in 20 European countries. Comments were answered, and the guideline was revised accordingly. The following procedures should be offered to women: 1) Amniotomy alone may be considered. 2) Women should be informed that there is no scientific evidence regarding the beneficial effects of immediate (<1 h) or delayed administration of oxytocin, although the first option may reduce the duration of labor. A joint decision is recommended, based on clinical judgment, and women's values and preferences. 3) A low-dose oxytocin regimen for labor augmentation should be considered. 4) Amniotomy should be considered before the administration of oxytocin infusion during the first stage of spontaneous labor. 5) Oxytocin augmentation for at least four hours with adequate uterine contractions should be considered, before an operative delivery is proposed, provided that fetal and maternal conditions are adequate.

• MeSH
• amniotomie MeSH
• dystokie * terapie   diagnóza   MeSH
• komplikace porodu * terapie   diagnóza   MeSH
• lidé MeSH
• oxytocin aplikace a dávkování   MeSH
• parita MeSH
• porodní děj MeSH
• těhotenství MeSH
• uterotonika aplikace a dávkování   MeSH
• vedení porodu MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Bordetella pertussis isolates which do not express some of acellular pertussis vaccine (aPv) antigens, e.g. pertactin (PRN), have been increasingly reported in countries using aPvs. In Finland, primary pertussis vaccination with whole-cell vaccine was replaced by aPv containing pertussis toxin (PT) and filamentous hemagglutinin (FHA) in 2005 and then by aPv containing PT, FHA, and PRN in 2009. We aimed to study alterations in the expression of FHA, PRN, and PT, three antigens included in aPvs and adenylate cyclase toxin (ACT) not included in current aPvs, among Finnish isolates collected during 1991-2020. METHODS: Of 904 isolates collected by the Finnish Reference Laboratory for Pertussis during 1991-2020, 302 were randomly included. An adapted, monoclonal antibody based, antigen expression ELISA, including the culture of B. pertussis in Stainer-Scholte medium, was performed to quantify the expression of ACT, FHA, PRN, and PT of each isolate. ACT activity was also measured for 16 isolates. Arbitrary units were used for comparing levels of each antigen expression of isolates grouped in every five years. FINDINGS: Following the implementation of aPv in 2005, B. pertussis isolates exhibited a 1.75-fold increase for FHA (p < 0.001) and a 1.5-fold increase for ACT (p < 0.0041) expression until 2020. No FHA or ACT deficient isolates were detected. As the number of PRN deficient isolates has significantly increased with the time, the amount of PRN produced by the positive isolates has also started to decrease, especially after the use of aPv containing PRN. During this period, fluctuations in PT expression were observed. INTERPRETATION: The study demonstrated that in response to aPv-induced selection pressure, different types of selection of B. pertussis has occurred. For FHA and ACT, a steady increase in their production is observed, whereas the frequency of PRN deficient isolates is increased with time.

• MeSH
• acelulární vakcíny imunologie   MeSH
• adenylátcyklasový toxin imunologie   MeSH
• antigeny bakteriální * imunologie   MeSH
• bakteriální adheziny MeSH
• Bordetella pertussis * imunologie   izolace a purifikace   MeSH
• ELISA MeSH
• faktory virulence rodu Bordetella imunologie   MeSH
• lidé MeSH
• pertuse * prevence a kontrola   imunologie   mikrobiologie   MeSH
• pertusová vakcína * imunologie   aplikace a dávkování   MeSH
• pertusový toxin imunologie   MeSH
• proteiny vnější bakteriální membrány imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Finsko MeSH