INTRODUCTION/AIMS: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. METHODS: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.
- MeSH
- autoprotilátky krev MeSH
- činnosti denního života MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- imunologické faktory terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- intravenózní imunoglobuliny * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- myasthenia gravis * farmakoterapie MeSH
- prospektivní studie 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 II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
PURPOSE OF REVIEW: This review explores the design and endpoints of perioperative platforms in clinical trials for muscle-invasive bladder cancer (MIBC). RECENT FINDINGS: The choice of clinical trial design in perioperative platforms for MIBC must align with specific research objectives to ensure robust and meaningful outcomes. Novel designs in perioperative platforms for MIBC integrate bladder-sparing approaches. Primary endpoints such as pathological complete response and disease-free survival are highlighted for their role in expediting trial results in perioperative setting. Incorporating patient-reported outcomes is important to inform healthcare decision makers about the outcomes most meaningful to patients. Given the growing body of evidence, potential biomarkers, predictive and prognostic tools should be considered and implemented when designing trials in perioperative platforms for MIBC. SUMMARY: Effective perioperative platforms for MIBC trials are critical in enhancing patient outcomes. The careful selection and standardization of study designs and endpoints in the perioperative platform are essential for the successful implementation of new therapies and the advancement of personalized treatment approaches in MIBC.
- MeSH
- cystektomie metody škodlivé účinky MeSH
- invazivní růst nádoru * MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- nádory močového měchýře * chirurgie patologie terapie mortalita MeSH
- perioperační péče metody normy MeSH
- stanovení cílového parametru MeSH
- výsledek terapie MeSH
- výzkumný projekt MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury. METHODS: This randomised, double-blind, placebo-controlled phase 2b clinical trial was done at 13 hospitals in the Czech Republic, Germany, Spain, and Switzerland. Patients aged 18-70 years with acute, complete or incomplete cervical spinal cord injury (neurological level of injury C1-C8) within 4-28 days of injury were eligible for inclusion. Participants were initially randomly assigned 1:1 to intrathecal treatment with 45 mg NG101 or placebo (phosphate-buffered saline); 18 months into the study, the ratio was adjusted to 3:1 to achieve a final distribution of 2:1 to improve enrolment and drug exposure. Randomisation was done using a centralised, computer-based randomisation system and was stratified according to nine distinct outcome categories with a validated upper extremity motor score (UEMS) prediction model based on clinical parameters at screening. Six intrathecal injections were administered every 5 days over 4 weeks, starting within 28 days of injury. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was change in UEMS at 6 months, analysed alongside safety in the full analysis set. The completed trial was registered at ClinicalTrials.gov, NCT03935321. FINDINGS: From May 20, 2019, to July 20, 2022, 463 patients with acute traumatic cervical spinal cord injury were screened, 334 were deemed ineligible and excluded, and 129 were randomly assigned to an intervention (80 patients in the NG101 group and 49 in the placebo group). The full analysis set comprised 78 patients from the NG101 group and 48 patients from the placebo group. 107 (85%) patients were male and 19 (15%) patients were female, with a median age of 51·5 years (IQR 30·0-60·0). Across all patients, the primary endpoint showed no significant difference between groups (with UEMS change at 6 months 1·37 [95% CI -1·44 to 4·18]; placebo group mean 19·20 [SD 11·78] at baseline and 30·91 [SD 15·49] at day 168; NG101 group mean 18·23 [SD 15·14] at baseline and 31·31 [19·54] at day 168). Treatment-related adverse events were similar between groups (nine in the NG101 group and six in the placebo group). 25 severe adverse events were reported: 18 in 11 (14%) patients in the NG101 group and seven in six (13%) patients in the placebo group. Although no treatment-related fatalities were reported in the NG101 group, one fatality not related to treatment occurred in the placebo group. Infections were the most common adverse event affecting 44 (92%) patients in the placebo group and 65 (83%) patients in the NG101 group. INTERPRETATION: NG101 did not improve UEMS in patients with acute spinal cord injury. Post-hoc subgroup analyses assessing UEMS and Spinal Cord Independence Measure of self-care in patients with motor-incomplete injury indicated potential beneficial effects that require investigation in future studies. FUNDING: EU program Horizon2020; Swiss State Secretariat for Education, Research and Innovation; Wings for Life; the Swiss Paraplegic Foundation; and the CeNeReg project of Wyss Zurich (University of Zurich and Eidgenössische Technische Hochschule Zurich).
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- krční mícha * zranění MeSH
- krční obratle MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Nogo proteiny * MeSH
- poranění míchy * farmakoterapie MeSH
- senioři MeSH
- spinální injekce * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Although there is growing evidence of the association between gender and early diagnosis of preclinical Alzheimer's disease, little attention has been given to the enrolment ratio of men and women in clinical trials and data reporting. METHODS: This study aims to analyze gender differences in sociodemographic factors associated with the willingness to participate in clinical trials and undergo specific procedures in the context of an Alzheimer's disease prevention research cohort. 2544 cognitively unimpaired participants from the ALFA parent cohort (age 45-75 years) of the Barcelonaβeta Brain Research Center were contacted through a structured phone call to determine their willingness to participate in Alzheimer's disease clinical trials and undergo trial-related procedures (magnetic resonance imaging, lumbar puncture, positron emission tomography, and cognitive assessment). Sociodemographic data on education, occupational attainment, civil and caregiver status were gathered. Stepwise logistic regression models were performed in order to study the interaction between gender and sociodemographic factors in the willingness to participate in clinical trials and to undergo clinical trial-related procedures. RESULTS: 1,606 out of the 2,544 participants were women (63.1%). Women were significantly younger and had lower educational attainment compared with men. In addition, women were more likely to be caregivers, single and unemployed. Women showed a significantly lower willingness than men to participate in a clinical trial (p = 0.003) and to undergo a lumbar puncture (p < 0.001). Single women were less willing to participate in clinical trials than single men (p = 0.041). Regarding clinical trial-related procedures, women with higher years of education were significantly less willing to undergo a lumbar puncture (p = 0.031). CONCLUSION: We found gender differences regarding the sociodemographic factors that predict the willingness to participate in clinical trials and to undergo clinical trial-related procedures. Our results highlight the urgent need to design recruitment strategies accounting for gender-related factors, particularly those related to marital status and education.
- MeSH
- Alzheimerova nemoc * psychologie MeSH
- klinické zkoušky jako téma * psychologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- pohlavní dimorfismus MeSH
- senioři MeSH
- sexuální faktory MeSH
- stupeň vzdělání MeSH
- výběr pacientů MeSH
- zapojení pacienta psychologie statistika a číselné údaje MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Onemocnění ledvin je u pacientů s mnohočetným myelomem časté. Z důvodu nepříznivé prognózy nebyli pacienti s nezvratným selháním ledvin při mnohočetném myelomu akceptováni k transplantaci ledviny. Současné terapeutické režimy mnohočetného myelomu významně zlepšily přežití těchto pacientů, a proto jsou častěji referováni k transplantaci ledviny. Recentně publikovaná data podporují přístup, že určitá kohorta pacientů může z transplantace ledviny profitovat. Jedná se zejména o pacienty bez zásadních komorbidit s trvající remisí mnohočetného myelomu, součástí jehož léčby byla transplantací kostní dřeně. Je nezbytný multidisciplinární přístup s individualizovaným posouzením transplantability. Tento přehledný článek sumarizuje poznatky týkající se možností transplantace ledviny u pacientů s mnohočetným myelomem.
Kidney disease is common in patients with multiple myeloma. Due to an unfavourable prognosis, patients with end-stage kidney disease in multiple myeloma were not accepted for kidney transplantation. Current therapeutic options for multiple myeloma have significantly improved the survival of these patients, thus more individuals are being referred for kidney transplantation. Recently published data support that a certain cohort of patients may benefit from transplantation. These are mainly patients with stable remission of multiple myeloma, whose treatment included stem cell transplantation. A multidisciplinary approach with an individualised assessment of transplantability is necessary. This review summarises recent knowledge regarding the possibility of kidney transplantation in patients with multiple myeloma.
- MeSH
- lidé MeSH
- mnohočetný myelom * komplikace MeSH
- renální insuficience MeSH
- transplantace ledvin * MeSH
- výběr pacientů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Východiska: V tradičním pojetí vnímání univerzit byl dlouhou dobu akcentován model první a druhé role. První role univerzit byla vždy spjata se samotným vzděláváním. Druhá role pak s vědecko-výzkumnou činností. Třetí role univerzit je dnes již zakotvena jako nedílná součást dlouhodobých záměrů většiny univerzit. Hlavní myšlenkou je především skutečnost, že univerzity, fakulty a její parciální pracoviště by se neměly uzavírat do sebe samých, ale měly by zaujmout aktivní roli ve veřejném prostoru. V současnosti jedním z modelů naplňování třetí role je pojetí univerzity, která může být pojímána nebo se může profilovat jako podnikatelský subjekt – triple helix model. Tímto může docházet k větší propojenosti univerzit s aplikační a podnikatelskou praxí. Tato skutečnost následně umožňuje komercializovat výsledky vědecko-výzkumné činnosti, podílet se na pokrytí nákladových položek a případně generovat zisk konkrétních univerzitních pracovišť. Cíle: Cílem práce je představení konceptu Průmysl 4.0, jeho vliv a přesahy do oblasti práce a vzdělávání, včetně naplňování třetí role univerzit. V analytické části je cílem představit konkrétní příklady „dobré praxe“ v realizaci naplňování třetí role v rámci činnosti univerzitního vědeckotechnického parku a ve spolupráci s dalšími významnými univerzitními pracovišti v ČR a subjekty z podnikatelského prostředí. Závěry: Předložená práce naznačuje možnosti propojení univerzitního prostředí a vybraných pracovišť s podnikatelským prostředím na konkrétních příkladech dobré praxe. Jsou předloženy možnosti vzájemné spolupráce různých univerzitních pracovišť s komerční sférou, ve snaze naplňovat třetí roli univerzit v kontextu modelu triple helix.
Background: The traditional perception of universities has long emphasised the first and second role model. The first role of universities has always been linked to education itself. The second role has been linked to scientific research. The third role of universities is now embedded as an integral part of the long-term goals of most universities. Above all, the main idea is that universities, faculties and their departments should not be self-contained but should take an active role in the public sphere. Currently, one model for fulfilling the third role is the notion of a university that can be conceived or profile itself as a business entity - the triple helix model. This may lead to greater interconnection between universities and application and business practice. This in turn enables the commercialization of the results of scientific research activities, participation in cost recovery and possibly profit generation for specific university departments. Objective: The aim of the thesis is to introduce the concept of Industry 4.0, its impact and overlaps in the field of work and education, including the fulfilment of the third role of universities. In the analytical part, the aim is to present concrete examples of "good practice" in the implementation of the third role within the activities of the university science and technology park and in cooperation with other major universities in the Czech Republic and entities from the business environment. Conclusions: The presented work indicates the possibilities of linking the university environment and selected departments with the business environment on specific examples of good practice. The possibilities of mutual cooperation between different university departments and the commercial sphere are presented, in an attempt to fulfil the third role of universities in the context of the triple helix model.
AIM: This systematic review aims to identify methodological and ethical challenges in designing and conducting research at the end of life from the perspective of researchers and provide a set of recommendations. BACKGROUND: Conducting research with patients and family carers facing end-of-life issues is ethically and methodologically complex. DESIGN: A systematic review was conducted. DATA SOURCES: Four databases (MEDLINE, EMBASE, CINAHL, PsycInfo) were searched from inception until the end of 2021 in February 2022. REVIEW METHODS: The Preferred Reporting Items for Systematic Reviews was followed, and the JBI Approach to qualitative synthesis was used for analysis. RESULTS: Seventeen of 1983 studies met inclusion criteria. Data were distilled to six main themes. These included (1) the need for flexibility at all stages of the research process; (2) careful attention to timing; (3) sensitivity in approach; (4) the importance of stakeholder collaboration; (5) the need for unique researcher skills; and (6) the need to deal with the issue of missing data. CONCLUSION: The findings illuminate several considerations that can inform training programmes, ethical review processes and research designs when embarking on research in this field.
- MeSH
- kvalitativní výzkum * MeSH
- lidé MeSH
- péče o umírající * etika MeSH
- výzkumný projekt * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
Cíl: Vyhledat a popsat intervence koordinované sestrou a jejich vliv na skóre kvality života pacientů se stabilní ischemickou chorobou srdeční (ICHS) včetně popisu koncepčního rámce intervence a nejdůležitějších aspektů poskytované ošetřovatelské péče. Metodika: Přehledová studie. Byly prozkoumány databáze PubMed, Scopus, Web of Science, ProQuest, Google Scholar. Pro stanovení základních komponent byla položena klinická otázka pomocí akronymu PICO (Patient/Problem, Intervention, Comparison and Outcome). Populaci tvořili pacienti se stabilní ICHS (P), edukace/intervence koordinovaná sestrou byla určena jako intervence (I), studie zahrnovaly kontrolní skupinu s rutinní péčí pro porovnání (C), sledovaným výsledkem bylo skóre kvality života pacientů (O). Výsledkem rešerše bylo celkem 448 studií publikovaných v letech 2013–2023. Výsledky: Do závěrečného přehledu bylo zahrnuto 24 studií, které jednoznačně vycházely ze sestrou koordinovaných intervencí ve vztahu ke kvalitě života pacientů se stabilní ICHS. Pro měření kvality života před a po intervenci byly využity různé nástroje, případně jejich kombinace. Koncepční rámce intervencí vycházely z ošetřovatelských modelů a z managementu péče o chronicky nemocné. Všechny studie uvedly zlepšení skóre kvality života pacientů u intervenční skupiny po provedení intervence. Závěr: Ve vybraných studiích bylo prokázáno, že intervenční programy kardiovaskulární rehabilitace vedené sestrou vedly ke zlepšení skóre kvality života pacientů se stabilní ICHS. Za důležité aspekty těchto intervencí považujeme péči o psychický stav pacienta, jeho aktivní zapojení do péče a také komplexnost, kontinuitu a personalizaci poskytované péče.
Aim: To find and describe nurse-coordinated interventions and their effect on quality of life scores of patients with stable coronary artery disease (CAD), including a description of the conceptual framework of the intervention and the most important aspects of the nursing care provided. Methodology: A review study. PubMed, Scopus, Web of Science, ProQuest, Google Scholar databases were studied. To determine the basic components, a clinical question was asked using the acronym PICO (Patient/Problem, Intervention, Comparison and Outcome). The population consisted of patients with stable CAD (P), the nurse-coordinated education/intervention was designated as the intervention (I), the studies included a control group with routine care for comparison (C), and the observed outcome was the patient quality of life score (O). The result of the search was a total of 448 studies published in the years 2013-2023. Results: The final review included 24 studies that were clearly based on nurse-coordinated interventions in relation to the quality of life of patients with stable CAD. Various instruments, or combinations thereof, were used to measure the quality of life before and after the intervention. The conceptual frameworks of the interventions were based on nursing models and chronic disease management. All studies reported an improvement in patient quality of life scores in the intervention group after the intervention. Conclusion: In selected studies, nurse-led cardiovascular rehabilitation intervention programs have been shown to improve quality of life scores in patients with stable CAD. The care of the patient's mental state, patient engagement, as well as the comprehensiveness, continuity and personalization of the care provided are considered to be important aspects of these interventions.
BACKGROUND: Unmet medical needs remain in patients with red blood cell transfusion-dependent (RBC-TD) lower-risk myelodysplastic syndromes (LR-MDS) who are not responding to or are ineligible for erythropoiesis-stimulating agents (ESAs). Imetelstat, a competitive telomerase inhibitor, showed promising results in a phase 2 trial. We aimed to compare the RBC transfusion independence (RBC-TI) rate with imetelstat versus placebo in patients with RBC-TD LR-MDS. METHODS: In phase 3 of IMerge, a double-blind, placebo-controlled trial conducted in 118 sites including university hospitals, cancer centres, and outpatient clinics in 17 countries, patients (aged ≥18 years) with ESA-relapsed, ESA-refractory, or ESA-ineligible LR-MDS (low or intermediate-1 risk disease as per International Prognostic Scoring System [IPSS] criteria) were randomly assigned via a computer-generated schedule (2:1) to receive imetelstat 7·5 mg/kg or placebo, administered as a 2-h intravenous infusion, every 4 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Randomisation was stratified by previous RBC transfusion burden and IPSS risk group. Patients, investigators, and those analysing the data were masked to group assignment. The primary endpoint was 8-week RBC-TI, defined as the proportion of patients without RBC transfusions for at least 8 consecutive weeks starting on the day of randomisation until subsequent anti-cancer therapy, if any. Primary efficacy analyses were performed in the intention-to-treat population, and safety analyses were conducted in patients who received at least one dose of trial medication or placebo. This trial is registered with ClinicalTrials.gov (NCT02598661; substudy active and recruiting). FINDINGS: Between Sept 11, 2019, and Oct 13, 2021, 178 patients were enrolled and randomly assigned (118 to imetelstat and 60 to placebo). 111 (62%) were male and 67 (38%) were female. 91 (77%) of 118 patients had discontinued treatment by data cutoff in the imetelstat group versus 45 (75%) in the placebo group; a further one patient in the placebo group did not receive treatment. Median follow-up was 19·5 months (IQR 12·0-23·4) in the imetelstat group and 17·5 months (12·1-22·7) in the placebo group. In the imetelstat group, 47 (40% [95% CI 30·9-49·3]) patients had an RBC-TI of at least 8 weeks versus nine (15% [7·1-26·6]) in the placebo group (rate difference 25% [9·9 to 36·9]; p=0·0008). Overall, 107 (91%) of 118 patients receiving imetelstat and 28 (47%) of 59 patients receiving placebo had grade 3-4 treatment-emergent adverse events. The most common treatment-emergent grade 3-4 adverse events in patients taking imetelstat were neutropenia (80 [68%] patients who received imetelstat vs two [3%] who received placebo) and thrombocytopenia (73 [62%] vs five [8%]). No treatment-related deaths were reported. INTERPRETATION: Imetelstat offers a novel mechanism of action with durable transfusion independence (approximately 1 year) and disease-modifying activity for heavily transfused patients with LR-MDS who are not responding to or are ineligible for ESAs. FUNDING: Janssen Research & Development before April 18, 2019, and Geron Corporation thereafter.
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- erytropoéza MeSH
- lidé MeSH
- mladiství MeSH
- myelodysplastické syndromy * farmakoterapie MeSH
- oligonukleotidy * MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- trombocytopenie * farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
Diagnostic work-up and risk stratification in patients with bladder cancer before and after treatment must be refined to optimize management and improve outcomes. MRI has been suggested as a non-invasive technique for bladder cancer staging and assessment of response to systemic therapy. The Vesical Imaging-Reporting And Data System (VI-RADS) was developed to standardize bladder MRI image acquisition, interpretation and reporting and enables accurate prediction of muscle-wall invasion of bladder cancer. MRI is available in many centres but is not yet recommended as a first-line test for bladder cancer owing to a lack of high-quality evidence. Consensus-based evidence on the use of MRI-VI-RADS for bladder cancer care is needed to serve as a benchmark for formulating guidelines and research agendas until further evidence from randomized trials becomes available.
