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INTRODUCTION: Currently, limited data are available on long-term use of dupilumab to treat atopic dermatitis (AD) in a multinational real-world setting. The aim of this analysis was to report the interim 1-year data for patients with AD enrolled in the GLOBOSTAD registry, including treatment patterns, dupilumab effectiveness and safety, and healthcare burden. METHODS: GLOBOSTAD is an ongoing, 5-year, multinational, prospective, observational study of adult/adolescent (aged ≥ 12 years at baseline) patients with AD who initiated dupilumab in real-world settings according to their local country-specific prescribing guidelines. Outcomes were evaluated at baseline and at 3, 6 and 12 months and included Eczema Area and Severity Index (EASI) total score, SCORing Atopic Dermatitis (SCORAD) total score, percent body surface area (BSA) affected, Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI) total score for adults or Children's Dermatology Life Quality Index (CDLQI) total score for adolescents and pruritus Numeric Rating Scale (NRS) total score. RESULTS: At the interim 1-year cut-off (March 2023), 955 patients were enrolled in GLOBOSTAD, and follow-up data were obtained from 903 patients. After dupilumab initiation, mean improvements in effectiveness outcome measures from baseline to month 3 were EASI from 25.1 to 6.1, SCORAD 59.3 to 25.3, POEM 19.7 to 8.7, DLQI 13.7 to 5.3, CDLQI 12.2 to 2.7 and pruritus NRS 6.3 to 2.5, with each measure exceeding the minimal clinically important difference. These positive changes in effectiveness outcomes were maintained or further improved through 12 months since treatment initiation. AD-related hospitalizations and emergency room or urgent care facility visits decreased from 11.1% to 1.7% from baseline to month 12. CONCLUSIONS: In a multinational real-world setting, dupilumab demonstrated rapid, robust and sustained effectiveness in patients with moderate-to-severe AD across multiple disease domains, including AD signs, symptoms, quality of life and emergency/urgent care visits. Safety was consistent with the known dupilumab safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03992417.
- MeSH
- atopická dermatitida * farmakoterapie MeSH
- dítě MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- kvalita života * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- prospektivní studie MeSH
- registrace MeSH
- stupeň závažnosti nemoci * MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
BACKGROUND: Head tremor poses diagnostic problems, especially when present as an isolated or predominant symptom. OBJECTIVES: To assess how maneuvers activating upper limb postural tremor can help differentiate head tremor in essential tremor (ET) from dystonic tremor (DT) in cervical dystonia. METHODS: 48 patients with head tremor (25 ET, 23 DT), underwent clinical examination and accelerometric evaluation of head and upper limb tremor during routine tremor-inducing tasks. RESULTS: While accelerometric power and clinical scores of head tremor did not significantly differ between patient groups, task-induced variations revealed distinctions. ET patients exhibited increased head tremor power and clinical scores during forward outstretched and lateral wing-beating arm positions, unlike DT patients. Coherence between head and upper limb tremor remained consistent. Tremor stability index showed no significant differences. CONCLUSIONS: Task-induced changes in head tremor could aid in distinguishing between ET and DT. Further research is needed to refine diagnostic approaches for head tremor.
- MeSH
- akcelerometrie přístrojové vybavení metody MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- dystonie diagnóza patofyziologie MeSH
- esenciální tremor * diagnóza patofyziologie MeSH
- hlava * patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- paže * patofyziologie MeSH
- postura těla fyziologie MeSH
- senioři MeSH
- tortikolis diagnóza patofyziologie MeSH
- tremor * diagnóza patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: While anal cancer is a very rare oncological diagnosis representing less than 2% of lower gastrointestinal tract cancers, the incidence has doubled in the past 20 years. Radical radiochemotherapy with sequential or simultaneous boost is now the standard treatment modality. Interstitial HDR brachytherapy is one of the boost application options. Implementation of new radiotherapy techniques has resulted in improved therapeutic outcomes; however, it is still associated with acute and especially late toxicity. Gastrointestinal disorders and sexual dysfunction are the most frequent factors affecting the long-term quality of cured patients' lives. METHODS: A total of 96 patients consecutively treated between 2000 and 2022 with external beam radio-/chemotherapy and an interstitial brachytherapy boost for histologically verified nonmetastatic anal squamous cell carcinoma were evaluated. The median follow-up time was 15.4 years (range 13.4-17.3 years). The primary objective of the study was to assess local control (LC) and quality of life (QoL). The Czech versions of internationally validated EORTC questionnaires were used to evaluate life quality-the basic EORTC QOL-C30 v.3 and the specific QOL-ANL 27 questionnaire. RESULTS: Local control was 85.5% at 5 years, 83.4% at 10 years, 83.4% at 15 years, and 83.4% at 20 years, and there was no dependence on clinical stage. The most common forms of acute toxicity were cutaneous and hematological but were gastrointestinal for late toxicities. In the evaluation of quality of life, 80.5% of patients alive at the time participated. In the EORTC quality of life questionnaire C30 v.3, patients rated the functional scale score as 86.2 points (standard deviation [SD] = 12.6) and the symptom score as 15.5 points (SD = 12.5). The global health score achieved 68.4 points (SD = 23.6). The most common symptoms were fatigue with 25.6 points (SD = 20.2) and diarrhea with 19.0 points (SD = 27.8). In the QOL-ANL 27 questionnaire, symptom scales assessing bowel symptoms were scored 27.5 points (SD = 19) in non-stoma patients and 11.9 points (SD = 17.2) in stoma patients. In the single-item symptom scales, the highest scores were rated for frequency of urination with 26.4 points (SD = 30.8), need to be close to a toilet with 22.4 points (SD = 27.3), and self-cleaning more often with 25.3 points (SD = 31.8). In the functional scales assessing sex life and interest, men and women reported scores of 45.2 (SD = 23) and 45.5 points (SD = 19), respectively. CONCLUSION: Boost with interstitial HDR brachytherapy is an established safe method of anal cancer treatment, with excellent results and limited late toxicity. Functioning scales were rated relatively highly in QoL questionnaires, and the overall global health score was comparable to published data. Gastrointestinal difficulties, fatigue, and sexual dysfunction dominated the symptom scales in our cohort.
- MeSH
- brachyterapie * metody MeSH
- celková dávka radioterapie MeSH
- dospělí MeSH
- kvalita života * psychologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory anu * radioterapie psychologie patologie MeSH
- následné studie MeSH
- průzkumy a dotazníky MeSH
- radiační poranění * psychologie etiologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom * radioterapie patologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Pivotal studies with dupilumab demonstrated clinically relevant improvements in nasal polyp score, symptom score, and quality-of-life score in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: We evaluated the effectiveness of dupilumab in a large-scale CRSwNP cohort from 6 European tertiary-care centers. METHODOLOGY: Nasal polyp score, Sinonasal Outcome Test 22 score, visual analog scale for total sinus symptoms, loss of smell, and nasal blockage, and Asthma Control Test (ACT) score were collected from hospital records and assessed at baseline and again at 24 and 52 weeks' treatment with dupilumab in CRSwNP patients. Treatment effectiveness was evaluated in relation to demographic and lifestyle factors, sinus surgery history, presence of comorbidities, and blood eosinophil counts (BEC). Treatment response was evaluated according to European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) 2021 criteria. RESULTS: All patient outcomes improved at 24 and 52 weeks' treatment compared to baseline. Dupilumab showed effectiveness independent of age, sex, body mass index, smoking status, prior sinus surgery, presence of asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, allergy, or baseline BEC. A total of 92.5% and 94.4% showed an improvement in at least 1 EUFOREA criterion at 24 and 52 weeks, respectively; 54.4% and 68.2% met all 4 of the more stringent EUFOREA criteria at 24 and 52 weeks, respectively. CONCLUSIONS: Real-world evaluation of dupilumab effectiveness demonstrates a robust and sustained response in at least two thirds of patients at 52 weeks' treatment. Favorable treatment response was independent of the number of sinus surgery procedures, major comorbidities, or baseline systemic levels of type 2 inflammation.
- MeSH
- chronická nemoc MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- kohortové studie MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- nosní polypy * farmakoterapie imunologie MeSH
- rinosinusitida MeSH
- rýma * farmakoterapie MeSH
- senioři MeSH
- sinusitida * farmakoterapie 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
- Geografické názvy
- Evropa MeSH
BACKGROUND: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking. AIMS: To examine the usability of darvadstrocel therapy in managing perianal CD. METHODS: We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression. RESULTS: Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported. CONCLUSION: Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.
- MeSH
- Crohnova nemoc * terapie komplikace MeSH
- dospělí MeSH
- indukce remise MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- rektální píštěl * terapie etiologie MeSH
- retrospektivní studie MeSH
- spokojenost pacientů MeSH
- transplantace mezenchymálních kmenových buněk * metody škodlivé účinky MeSH
- výsledek terapie 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
- multicentrická studie MeSH
BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is an established treatment for achalasia with compelling midterm efficacy. In this study, we analyzed the long-term efficacy, sought predictors of failure, and comprehensively assessed post-POEM reflux. METHODS: We performed a retrospective analysis of a prospective database of patients undergoing POEM at a high-volume center from December 2012 to June 2023. Patients who had completed a 3-month follow-up were included. Efficacy was assessed at 3, 6, and 8 years using the Eckardt score (ES). An ES ≤2 was considered treatment success. At 3 months, gastroscopy, manometry, 24-hour pH monitoring, and fluoroscopy were performed, and gastroscopy was repeated at 2 and 3 years. At each visit, patients were assessed for reflux symptoms and quality of life. RESULTS: From 496 included patients, 3-, 6-, and 8-year follow-ups were completed in 302, 115, and 40 patients, respectively. The treatment success rates at 3, 6, and 8 years according to the Kaplan-Meier analysis were 90.2% (95% confidence interval [CI], 87.2-93.3), 82.3% (95% CI, 77.3-87.6), and 73.5% (95% CI, 64.8-83.5), respectively. Year of procedure was the only predictor of outcome. Fifty-three patients (10.7%) encountered failure or recurrence. Treatment success of redo-POEM (n = 20) at 1 year was significantly lower (62.9% [95% CI, 44.3-89.2] vs 96.9% [95% CI, 95.3-98.5], P < .001). At 3 months, 40.4% of patients had reflux esophagitis (RE), 43.6% of patients had an acid exposure time >4.5%, 39.2% of patients were using proton pump inhibitors (PPIs), but only 24.2% had reflux symptoms. At 2 to 3 years, 50.8% of patients took PPIs, whereas 39.6% were symptomatic. RE decreased to 20.2% at 6 years. CONCLUSIONS: The treatment success of POEM declines over time but remains sufficiently high in the long term. Experience with the procedure improves the outcome. Gastroesophageal reflux affects almost half of patients early after POEM and decreases substantially over time together with a rise in PPI use.
- MeSH
- achalázie jícnu * chirurgie patofyziologie MeSH
- časové faktory MeSH
- centra terciární péče MeSH
- dolní jícnový svěrač * chirurgie MeSH
- dospělí MeSH
- endoskopické operace přirozenými otvory * metody MeSH
- fluoroskopie MeSH
- gastroezofageální reflux * etiologie epidemiologie MeSH
- gastroskopie MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- manometrie MeSH
- monitorování jícnového pH MeSH
- následné studie MeSH
- pooperační komplikace * epidemiologie MeSH
- pyloromyotomie * metody MeSH
- recidiva MeSH
- retrospektivní studie 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
INTRODUCTION: This was a single-center pilot study that sought to describe an innovative use of 4DryField® PH (premix) for preventing the recurrence of intrauterine adhesions (IUAs) after hysteroscopic adhesiolysis in patients with Asherman's syndrome (AS). MATERIAL AND METHODS: Twenty-three patients with AS were enrolled and 20 were randomized (1:1 ratio) to intrauterine application of 4DryField® PH (n = 10) or Hyalobarrier® gel (n = 10) in a single-blind manner. We evaluated IUAs (American Fertility Society [AFS] score) during initial hysteroscopy and second-look hysteroscopy one month later. Patients completed a follow-up symptoms questionnaire three and reproductive outcomes questionnaire six months later. RESULTS: The demographic and clinical characteristics, as well as severity of IUAs, were comparable in both groups. The mean initial AFS score was 9 and 8.5 in the 4DryField® PH and Hyalobarrier® gel groups, respectively (p = .476). There were no between-group differences in AFS progress (5.9 vs. 5.6, p = .675), need for secondary adhesiolysis (7 vs. 7 patients, p = 1), and the follow-up outcomes. CONCLUSION: 4DryField® PH could be a promising antiadhesive agent for preventing the recurrence of IUAs, showing similar effectiveness and safety to Hyalobarrier® gel. Our findings warrant prospective validation in a larger clinical trial. CLINICAL TRIAL REGISTRY NUMBER: ISRCTN15630617.
- MeSH
- adheze tkání prevence a kontrola MeSH
- dospělí MeSH
- gely * MeSH
- gynatrézie prevence a kontrola MeSH
- hysteroskopie * metody MeSH
- jednoduchá slepá metoda MeSH
- kyselina hyaluronová aplikace a dávkování MeSH
- lidé MeSH
- nemoci dělohy prevence a kontrola chirurgie MeSH
- pilotní projekty MeSH
- recidiva MeSH
- sekundární prevence metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
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
Syndrom komplexní regionální bolesti (KRBS) je onemocnění s multifaktoriální patofyziologií, v níž se uplatňuje senzitizace centrálního a periferního nervového systému, zánět, genetické faktory, vegetativní nervový systém, autoimunitní reakce a psychika. Složitá a nejednoznačná patofyziologie KRBS komplikuje klinickou diagnostiku. Ta je založena na mezinárodně schválených Budapešťských kritériích, jež berou v úvahu přítomnost symptomů a vylučují alternativní příčiny. Terapeutický management vyžaduje multidisciplinární přístup se zaměřením na individuální léčebné plány včetně řešení psychologických faktorů. Tento článek poskytuje přehled aktualizací v diagnostice a léčbě KRBS. Nejnovější doporučení pro léčbu KRBS zdůrazňují důležitost včasné diagnózy a intervence.
Complex Regional Pain Syndrome (CRPS) is a disease with a multifactorial pathophysiology involving central and peripheral nervous system sensitization, inflammation, genetic factors, autonomic nervous system, autoimmune response, and psychological disposition. The complex and ambiguous pathophysiology of CRPS complicates clinical diagnosis. This is based on the internationally approved Budapest criteria, which take into account the presence of symptoms and exclude alternative causes. Therapeutic management requires a multidisciplinary approach with a focus on individual treatment plans including addressing psychological factors. This review provides an overview of updates in the diagnosis and treatment of CRPS. The most recent guidelines for the treatment of CRPS emphasize the importance of early diagnosis and intervention.
- Klíčová slova
- Budapešťská kritéria,
- MeSH
- diferenciální diagnóza MeSH
- komplexní regionální syndromy bolesti * diagnóza farmakoterapie patologie MeSH
- lidé MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: This study aimed to assess the mid-term effects of focused extracorporeal shockwave therapy (ESWT) on clinical symptoms and tendon structure in patellar tendinopathy. Ultrasound (US) evaluation and an innovative in vivo analysis of intra-tendinous morphology using validated spatial frequency analysis (SFA) software were employed to quantify the organization and density of collagen fascicles. METHODS: This prospective cohort study included 21 recreational athletes (mean age 29.9 ± 9.3 years) with chronic unilateral symptomatic patellar tendinopathy. ESWT was applied as monotherapy over four weekly sessions. Pain was assessed using the Numeric Rating Scale (NRS) and disease severity with the Victorian Institute of Sports Assessment - Patella (VISA-P) questionnaire. Morphological parameters, such as tendon diameter (TD), were assessed with US and analyzed using SFA software. The asymptomatic tendons served as controls. Follow-up assessments were conducted at the end of the treatment period and 3 months posttreatment. RESULTS: Baseline evaluations revealed increased TD in proximal part of the tendon ( P = 0.001) and decreased organization of collagen fascicles ( P = 0.013) in symptomatic tendons compared to asymptomatic controls. At the 3-month follow-up, symptomatic tendons showed significant reductions in TD ( P < 0.001) and improvements in both organization and density of collagen fascicles throughout various parameters - peak spatial frequency radius (PSFR) ( P = 0.024), P6 ( P = 0.05), Q6 ( P = 0.016), PPP ( P = 0.003). No significant morphological changes were observed in asymptomatic tendons. Clinical evaluations demonstrated significant reductions in NRS ( P < 0.001) and increases in Victorian Institute of Sports Assessment - Patella (VISA-P) scores ( P < 0.001) at all time points. CONCLUSION: The study suggests that ESWT may have the potential to induce positive structural changes in patellar tendinopathy, including improved organization and density of collagen fascicles. These findings indicate that ESWT could be a promising noninvasive approach to managing patellar tendinopathy, with observed improvements in clinical symptoms and tendon structure. However, further high-quality research is needed to confirm these results and establish their long-term efficacy.
- MeSH
- dospělí MeSH
- léčba mimotělní rázovou vlnou * metody MeSH
- lidé MeSH
- ligamentum patellae * diagnostické zobrazování patologie MeSH
- mladý dospělý MeSH
- prospektivní studie MeSH
- tendinopatie * terapie diagnostické zobrazování patologie MeSH
- ultrasonografie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH