Publikace, která se zaměřuje na různé aspekty dlouhodobé péče o pacienty, zejména o duševně nemocné. Určeno odborné veřejnosti.; První komplexní monografie u nás, týkající se tématu, které je trvale v popředí zdravotnické veřejnosti. Kniha je určena zejména praktickým lékařům, ošetřovatelskému personálu pobytových zařízení, činitelům v oblasti veřejného zdravotnictví. Publikace sleduje především dva cíle, a to přispět v českém prostředí k vymezení a pochopení agendy, závažnosti a aplikace dosud málo známého pojetí dlouhodobé péče jako 3. pilíře „péčové oblasti“ a za druhé upozornit na vybrané klinické a etické aspekty zdravotnické, především lékařské, ale také ošetřovatelské a rehabilitační praxe v rámci dlouhodobé péče, u jejích klientů/pacientů, včetně praxe v pobytových zařízeních.

• MeSH
• Long-Term Care MeSH
• Persons with Psychiatric Disorders MeSH
• Ethics, Medical MeSH
• Public Assistance MeSH
• Social Work MeSH
• Legislation, Medical MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• veřejné zdravotnictví
• sociologie
• NML Publication type
• kolektivní monografie

BACKGROUND: Aveir DR (Abbott, Abbott Park, IL) is a dual-chamber leadless pacemaker (LP) system with distinct atrial and ventricular LPs (ALP, VLP) that communicate wirelessly to deliver atrioventricular synchronous pacing. Success rates of these implant-to-implant (i2i) transmissions have not been systematically evaluated. OBJECTIVE: This study aims to evaluate chronic i2i success rates in a clinical setting. METHODS: Patients meeting standard dual-chamber pacing indications were enrolled and implanted with dual-chamber LP systems as part of a prospective international clinical trial (Aveir DR i2i Study). The percent of successful i2i transmissions from ALP-to-VLP (A-to-V) and VLP-to-ALP (V-to-A) were interrogated from LPs in de novo patients using the device programmer at implant, discharge, and at 1, 3, and 6 months postimplant (1M, 3M, 6M). RESULTS: A total of 399 patients completed device implant and i2i diagnostic interrogation (62% male; age 69 years; 65% sinus node dysfunction, 32% atrioventricular [AV] block). Median A-to-V and V-to-A i2i success rates exceeded 90% of beats at all time-points from implant to 6M. The minority of patients with A-to-V or V-to-A i2i success in <70% of beats at implant (A-to-V: 19% of patients, V-to-A: 31% of patients) showed roughly 40% improvement by 1M, with this minority dropping to roughly 5% of patients by 6M. Improvement in i2i communication success may be attributed to reprogramming of i2i setting levels, natural changes in dominant posture, and device stabilization. CONCLUSION: Wireless implant-to-implant communication in the new dual-chamber leadless pacemaker system demonstrated successful transmissions in >90% of beats throughout the 6-month evaluation period. Communication success improved significantly over time postimplant for specific subgroups. CLINICAL TRIAL REGISTRATION: Aveir DR i2i Study, ClinicalTrials.gov ID NCT05252702.

• MeSH
• Wireless Technology MeSH
• Equipment Design * MeSH
• Cardiac Pacing, Artificial methods   MeSH
• Pacemaker, Artificial * MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Prospective Studies MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

BACKGROUND: A detailed understanding of alterations in olanzapine pharmacokinetics during acute inflammatory states, associated with infections, remains lacking. This study aimed to investigate the impact of endotoxemia on the pharmacokinetics of olanzapine and desmethylolanzapine (DMO) in mice. METHODS: C57BL/6N mice received an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) or saline (controls), followed 24 hours later by single oral or intravenous doses of olanzapine or intravenous DMO. Concentrations and unbound fractions of olanzapine and DMO were measured in the plasma and brain homogenates. RESULTS: In LPS-injected mice, the area under the concentration-time curve (AUCs) for olanzapine increased 3.8-fold in the plasma and 5.2-fold in brain homogenates, in consequence of a higher absolute bioavailability of olanzapine (+200%), a lower plasma clearance (-34%), and a higher brain penetration ratio for the unbound drug relative to controls (Kp,uu,brain 6.2 vs. 4.1). LPS attenuated the hepatic mRNA expression of cytochrome P450 1A2 and the metabolism of olanzapine to DMO. However, the AUC of plasma DMO increased by 140% due to a 4.8-fold decrease in the plasma clearance of DMO. The brain penetration of DMO was minimal (Kp,uu,brain ≤ 0.051). The LPS-injected mice exhibited a downregulation of the hepatic and ileal mRNA expression of P-glycoprotein (Abcb1a), whereas the expression of Abcb1a and Abcb1b in the brain was upregulated. CONCLUSIONS: Endotoxemia notably increases olanzapine concentrations in the plasma and brain following oral administration in mice. Further studies should clarify whether altered pharmacokinetics results in adverse effects in acutely infected patients taking oral olanzapine.

• MeSH
• Antipsychotic Agents * pharmacokinetics   blood   administration & dosage   MeSH
• Administration, Oral MeSH
• Benzodiazepines * pharmacokinetics   blood   administration & dosage   MeSH
• Endotoxemia * metabolism   chemically induced   MeSH
• Lipopolysaccharides MeSH
• Brain * metabolism   drug effects   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Olanzapine pharmacokinetics   MeSH
• Inflammation * chemically induced   metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

AIMS: A dual-chamber leadless pacemaker (LP) system that employs distinct atrial and ventricular LP devices (ALP, VLP) has been introduced to clinical practice. Proprietary, low-energy, implant-to-implant (i2i) communication at each beat enables the devices to maintain synchronous atrioventricular sensing and pacing. We evaluated device longevities and contributing factors, such as i2i communication. METHODS AND RESULTS: Patients meeting dual-chamber pacing indications received the dual-chamber LP system as part of a prospective, multi-centre, international clinical trial (Aveir DR i2i Study, NCT05252702). Programming and diagnostics were interrogated from all de novo, non-revised, dual-chamber programmed devices at 12 months post-implant. This analysis included 302 patients (65% male; age 70 ± 13 years; weight 80 ± 19 kg; intrinsic heart rate 55 ± 7 bpm; 58% sinus node dysfunction, 27% atrioventricular block). At 12 months, devices were programmed to dual-chamber pacing (DDD(R) or DDI(R)) at a median 60 bpm rate, median 1.25 V pulse amplitude in ALP and 1.5 V in VLP, median 0.4 ms pulse width, and median i2i signal setting level 5 out of 7. Median ALP and VLP remaining battery longevities at 12 months were 4.3 and 9.1 years, with median total ALP and VLP longevities of 5.3 and 9.9 years. Base rate, pulse amplitude, pacing percentage, event rate, impedance, and i2i setting level all exhibited significant correlations with ALP and VLP longevities (P < 0.001). Programming i2i setting levels below 7 produced the greatest longevity savings. CONCLUSION: The first dual-chamber LP demonstrated adequate projected battery longevity after 12 months of use. Patient-specific device programming considerations, unique to leadless devices, may extend longevity.

• MeSH
• Atrioventricular Block therapy   diagnosis   physiopathology   MeSH
• Time Factors MeSH
• Equipment Design MeSH
• Cardiac Pacing, Artificial * methods   MeSH
• Pacemaker, Artificial * MeSH
• Middle Aged MeSH
• Humans MeSH
• Prospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Arrhythmias, Cardiac * therapy   diagnosis   physiopathology   MeSH
• Heart Rate MeSH
• Treatment Outcome MeSH
• Electric Power Supplies * MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Multicenter Study MeSH

Schizophrenia, a profoundly impactful neuropsychiatric disorder, has been the subject of extensive research using animal models. However, certain important aspects remain understudied, including assumed long-term consequences of psychotic episodes on negative symptoms development and progression. Addressing these limitations, we proposed a novel animal model in male rats based on early postnatal immune activation triggered by lipopolysaccharide (LPS), serving as the predisposing factor (1st hit). As the 2nd hit, representing psychotic-like episodes, we implemented a multi-episodic co-treatment with dizocilpine (MK-801) and amphetamine (AMP), spanning multiple developmental periods. The animals were tested in two social behavioral assays in adolescence and adulthood to investigate whether a social deficit would arise. In addition, we evaluated the level of oxytocin (OT), a neuropeptide relevant to social behavior, in selected brain regions. In the social interaction test, when animals could freely interact in the open field and express their social behavioral profile entirely, social behavior decreased in adolescent experimental animals. In the social approach test in the Y maze, all animals, irrespective of treatment, preferred conspecific over an indifferent object and novel rat over a familiar rat. Further, the results revealed that the OT content in the hypothalamus increased with age. In the proposed model, social interaction in the open field was decreased in adolescent but not in adult rats, indicating that the pharmacological manipulations caused only transient age-dependent changes. The study was thus in certain aspects successful in creating a novel approach to model social deficit potentially relevant to schizophrenia; other findings require further investigation.

• Publication type
• Journal Article MeSH

BACKGROUND: Lipopolysaccharide (LPS)-induced inflammation of lung tissues triggers irreversible alterations in the lung parenchyma, leading to fibrosis and pulmonary dysfunction. While the molecular and cellular responses of immune and connective tissue cells in the lungs are well characterized, the specific epithelial response remains unclear due to the lack of representative cell models. Recently, we introduced human embryonic stem cell-derived expandable lung epithelial (ELEP) cells as a novel model for studying lung injury and regeneration. METHODS: ELEPs were derived from the CCTL 14 human embryonic stem cell line through activin A-mediated endoderm specification, followed by further induction toward pulmonary epithelium using FGF2 and EGF. ELEPs exhibit a high proliferation rate and express key structural and molecular markers of alveolar progenitors, such as NKX2-1. The effects of Escherichia coli LPS serotype O55:B5 on the phenotype and molecular signaling of ELEPs were analyzed using viability and migration assays, mRNA and protein levels were determined by qRT-PCR, western blotting, and immunofluorescent microscopy. RESULTS: We demonstrated that purified LPS induces features of a hybrid epithelial-to-mesenchymal transition in pluripotent stem cell-derived ELEPs, triggers the unfolded protein response, and upregulates intracellular β-catenin level through retention of E-cadherin within the endoplasmic reticulum. CONCLUSIONS: Human embryonic stem cell-derived ELEPs provide a biologically relevant, non-cancerous lung cell model to investigate molecular responses to inflammatory stimuli and address epithelial plasticity. This approach offers novel insights into the fine molecular processes underlying lung injury and repair.

• MeSH
• Cell Line MeSH
• Antigens, CD metabolism   MeSH
• Endoplasmic Reticulum * metabolism   drug effects   MeSH
• Epithelial-Mesenchymal Transition * drug effects   MeSH
• Epithelial Cells * drug effects   metabolism   cytology   MeSH
• Cadherins * metabolism   MeSH
• Humans MeSH
• Human Embryonic Stem Cells * cytology   MeSH
• Lipopolysaccharides * pharmacology   MeSH
• Lung * cytology   MeSH
• Thyroid Nuclear Factor 1 MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Lipoprotein (a) [Lp(a)] has been recognized as an independent, inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, thus representing a major target of residual CV risk. Currently, no drug has been officially approved for lowering Lp(a) levels, and in clinical practice, Lp(a) is mainly used to (re)define CV risk, particularly in individuals at borderline CV risk and people with a family history of premature coronary heart disease, according to various guidelines. Specific Lp(a)-targeted antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) agents have been developed to produce substantial Lp(a) reductions via the inhibition of apo(a) synthesis in the liver. These drugs are conjugated to N-acetylgalactosamine (GalNAc) to ensure their binding to asialoglycoproteins, which are specifically expressed on the surface of the hepatocytes. Such drugs include pelacarsen (an injectable ASO) and olpasiran, zerlasiran, and lepodisiran (injectable siRNA agents). Muvalaplin represents another therapeutic option to lower Lp(a) levels, since it is an oral selective small molecule inhibitor of Lp(a) formation, thus potentially exerting certain advantages in terms of its clinical use. The present narrative review summarizes the available clinical data on the efficacy and safety of these investigational Lp(a)-lowering therapies, as reported in phase 1 and 2 trials. The effects of these drugs on other [aside from Lp(a)] lipid parameters are also discussed. The phase 3 CV trial outcomes are ongoing for some of these agents (i.e., pelacarsen, olpasiran, and lepodisiran) and are briefly mentioned. Overall, there is an urgent need for evidence-based guidelines on Lp(a) reduction in daily clinical practice, following the results of the phase 3 CV trials, as well as for establishing the ideal Lp(a) quantification method (i.e., using an apo(a) isoform-independent assay with appropriate calibrators, reporting the Lp(a) level in molar units).

• Publication type
• Journal Article MeSH
• Review 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
• Vaccines, Acellular immunology   MeSH
• Adenylate Cyclase Toxin immunology   MeSH
• Antigens, Bacterial * immunology   MeSH
• Adhesins, Bacterial MeSH
• Bordetella pertussis * immunology   isolation & purification   MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Virulence Factors, Bordetella immunology   MeSH
• Humans MeSH
• Whooping Cough * prevention & control   immunology   microbiology   MeSH
• Pertussis Vaccine * immunology   administration & dosage   MeSH
• Pertussis Toxin immunology   MeSH
• Bacterial Outer Membrane Proteins immunology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Finland MeSH

There is striking evidence that a high lipoprotein(a) [Lp(a)] concentration is a strong, independent, and causal cardiovascular risk factor. However, Lp(a) testing rates are very low (1 %-2 %) despite the fact that 1 in 5 individuals have elevated Lp(a) concentrations. The Brussels International Declaration on Lp(a) Testing and Management was co-created by the Lp(a) International Task Force and global leaders at the Lp(a) Global Summit, held in Brussels, Belgium, on March 24-25, 2025. The event, organized by FH Europe Foundation, brought together scientific experts, people with the lived experience of elevated Lp(a) and policy makers from the European Institutions and World Health Organization. The World Heart Federation, Global Heart Hub, and European Alliance for Cardiovascular Health and scientific organizations such as European Atherosclerosis Society, and International Atherosclerosis Society were formal partners. The Summit was hosted by a Member of the European Parliament, Romana Jerković, and held under the patronage of the Polish presidency of the Council of the European Union. The Declaration calls for 1) integration of Lp(a) testing and management into Global, European and National Cardiovascular Health Plans; 2) appropriate investment, policy and programmes in targeting Lp(a) testing and management based on a recent study demonstrating the substantial overall cost-saving to health systems across the globe; 3) political commitment to mandate systematic Lp(a) testing at least once during a person's lifetime, ideally at an early age, with full reimbursement; 4) incorporation of Lp(a) test results in the context of a person's cardiovascular risk assessment, with development of personalised cardiovascular health roadmaps as needed, without fear of dredit aiscrimination; 5) investment in public and healthcare professional education to increase awareness of Lp(a) and its impact on cardiovascular health.

• MeSH
• Biomarkers blood   MeSH
• Risk Assessment MeSH
• Cardiovascular Diseases * blood   diagnosis   prevention & control   epidemiology   MeSH
• Consensus MeSH
• Humans MeSH
• Lipoprotein(a) * blood   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Úvod: Inhibícia aktivity proproteín konvertázy subtilizín/kexín typu 9 predstavuje účinnú stratégiu na zníženie LDL cholesterolu (LDL-C), ktorý je jedným z hlavných kardiovaskulárnych rizikových faktorov. Inklisiran, prvá malá interferujúca RNA cielená na PCSK9, preukázal v klinických štúdiách zníženie LDL-C o 50 %. Ciele: Cieľom tejto štúdie bolo opísať účinky inklisiranu v reálnych klinických podmienkach spolu s prvými klinickými skúsenosťami s jeho používaním na Slovensku. Metódy: V tejto observačnej štúdii bolo na liečbu inklisiranom vybraných 36 pacientov v rámci štandardných klinických vyšetrení, postupov a úhrady zo zdravotného poistenia. U každého pacienta sa pred podaním žiadosti o schválenie terapie vykonalo štandardné hodnotenie lipidového profilu a stanovenie vysokosenzitívneho C-reaktívneho proteínu (hsCRP), ktoré sa zopakovalo mesiac po podaní dvoch dávok inklisiranu. Priemerná zmena hladín lipidového profilu bola vypočítaná u každého pacienta, ktorý absolvoval tretiu dávku inklisiranu. Výsledky: Liečba inklisiranom bola schválená pre 36 pacientov, z toho 27 s aterosklerotickým ochorením koronárnych artérií a 9 po prekonaní cievnej mozgovej príhody. Súbor zahŕňal 1 pacienta intolerantného na statíny, 28 pacientov na maximálnej dávke statínov a 7 na zníženej dávke. Po 3 mesiacoch sa hladina LDL-C znížila o 57,5 %, hsCRP na 1,2 mg/dl a lipoproteín(a) o 14,3 ± 6,4 %. Bezpečnostné výsledky boli v súlade s klinickými štúdiami – mierna bolesť v mieste vpichu sa vyskytla u 26 pacientov a chrípkové príznaky u 3 pacientov. Záver: Inklisiran preukázal účinné zníženie hladín LDL-C a hsCRP, pričom výsledky mierne prevýšili klinické štúdie. Redukcia lipoproteínu(a) sa medzi pacientmi líšila. Bezpečnostný profil bol v súlade s očakávaniami, čo potvrdzuje potenciál inklisiranu pre širšie klinické využitie.

Background: Inhibiting proprotein convertase subtilisin/kexin type 9 activity is an effective strategy to lower LDL cholesterol (LDL-C), a major cardiovascular risk factor. Inclisiran, the first small interfering RNA targeting PCSK9, has shown a 50% LDL-C reduction in clinical trials. Aims: The aim of this study was to describe the effects of inclisiran in real-world clinical settings, along with the first clinical experiences of its use in Slovakia. Methods: In this observational study, 36 patients were selected for inclisiran therapy as part of standard clinical assessments, procedures, and reimbursement from public health insurance. Each patient underwent a standard lipid profile assessment and high-sensitivity C-reactive protein (hsCRP) testing before submitting applications for therapy approval, and again one month after receiving two doses of inclisiran. The average change in lipid profile levels was calculated for each patient who completed the third dose of inclisiran. Results: Inclisiran therapy was approved for 36 patients, including 27 with athero­sclerotic coronary artery disease and 9 with prior strokes. The cohort included 1 statin-intolerant patient, 28 on maximum statin doses, and 7 on reduced doses. After 3 months, LDL-C dropped by 57.5%, hsCRP to 1.2mg/dL, and lipoprotein(a) by 14.3 ± 6.4%. Safety outcomes mirrored clinical trials, with mild injection-site pain in 26 cases and flu-like symptoms in 3. Conclusions: Inclisiran demonstrated an effective reduction in LDL-C and hsCRP levels, slightly exceeding clinical trial outcomes, but lipoprotein(a) reductions varied among patients. Safety was consistent with expectations, confirming inclisiran's potential for broader clinical use.

• Keywords
• inclisiran,
• MeSH
• C-Reactive Protein analysis   drug effects   MeSH
• Adult MeSH
• Dyslipidemias * drug therapy   MeSH
• Hypolipidemic Agents administration & dosage   MeSH
• Cholesterol, LDL analysis   drug effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lipoprotein(a) analysis   drug effects   MeSH
• RNA, Small Interfering * administration & dosage   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Clinical Study MeSH