BACKGROUND: MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD-MUC1 patients produce approximately 50% of normal mucin-1. METHODS: To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths. RESULTS: Surveys were emailed to 637 individuals, with responses from 89 ADTKD-MUC1 and 132 ADTKD-UMOD individuals. 19/83 (23%) ADTKD-MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD-UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD-MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD-UMOD, with OR 9.21 (95%CI 1.22-69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD-MUC1 individuals was 7.06 ± 4.12 vs. 10.21 ± 4.02 U/mL (P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD-MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD-UMOD individuals (0.6%) (P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD-MUC1 8.4 (2.9-29.5), kidney transplant 5.5 (1.6-9.1), body mass index (kg/m2) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1). CONCLUSIONS: Individuals with ADTKD-MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD-UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible.

• Klíčová slova
• Autosomal Dominant Tubulointerstitial kidney disease, CA15-3, COVID-19, MUC1, Mucin-1, UMOD,
• MeSH
• COVID-19 * mortalita   genetika   MeSH
• dospělí MeSH
• intersticiální nefritida genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mucin 1 * krev   MeSH
• mutace * MeSH
• registrace MeSH
• SARS-CoV-2 genetika   MeSH
• senioři MeSH
• uromodulin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• MUC1 protein, human MeSH Prohlížeč
• mucin 1 * MeSH
• UMOD protein, human MeSH Prohlížeč
• uromodulin MeSH

BACKGROUND: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. OBJECTIVE: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg). DESIGN: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success. RESULTS: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT-containing bismuth, metronidazole and tetracycline-plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness. CONCLUSION: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness. TRIAL REGISTRATION NUMBER: NCT02328131.

• Klíčová slova
• ANTIBIOTIC THERAPY, HELICOBACTER PYLORI - TREATMENT, HELICOBACTER THERAPY,
• MeSH
• amoxicilin terapeutické užití   aplikace a dávkování   MeSH
• antibakteriální látky * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• bismut * terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• Helicobacter pylori * účinky léků   MeSH
• infekce vyvolané Helicobacter pylori * farmakoterapie   MeSH
• inhibitory protonové pumpy * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• klarithromycin terapeutické užití   aplikace a dávkování   MeSH
• kombinovaná farmakoterapie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• metronidazol terapeutické užití   aplikace a dávkování   MeSH
• registrace * MeSH
• senioři MeSH
• tetracyklin terapeutické užití   aplikace a dávkování   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
• pozorovací studie MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• amoxicilin MeSH
• antibakteriální látky * MeSH
• bismut * MeSH
• inhibitory protonové pumpy * MeSH
• klarithromycin MeSH
• metronidazol MeSH
• tetracyklin MeSH

INTRODUCTION: The use of antidepressants in bipolar disorder (BD) remains contentious, in part due to the risk of antidepressant-induced mania (AIM). However, there is no information on the architecture of mood regulation in patients who have experienced AIM. We compared the architecture of mood regulation in euthymic patients with and without a history of AIM. METHODS: Eighty-four euthymic participants were included. Participants rated their mood, anxiety and energy levels daily using an electronic (e-) visual analog scale, for a mean (SD) of 280.8(151.4) days. We analyzed their multivariate time series by computing each variable's auto-correlation, inter-variable cross-correlation, and composite multiscale entropy of mood, anxiety, and energy. Then, we compared the data features of participants with a history of AIM and those without AIM, using analysis of covariance, controlling for age, sex, and current treatment. RESULTS: Based on 18,103 daily observations, participants with AIM showed significantly stronger day-to-day auto-correlation and cross-correlation for mood, anxiety, and energy than those without AIM. The highest cross-correlation in participants with AIM was between mood and energy within the same day (median (IQR), 0.58 (0.27)). The strongest negative cross-correlation in participants with AIM was between mood and anxiety series within the same day (median (IQR), -0.52 (0.34)). CONCLUSION: Patients with a history of AIM have a different underlying mood architecture compared to those without AIM. Their mood, anxiety and energy stay the same from day-to-day; and their anxiety is negatively correlated with their mood.

• Klíčová slova
• antidepressant‐induced mania (AIM), auto‐correlation, bipolar disorder, cross‐correlation, euthymia, mood regulation, time series analysis,
• MeSH
• afekt * účinky léků   MeSH
• antidepresiva * terapeutické užití   škodlivé účinky   MeSH
• bipolární porucha * farmakoterapie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mánie * farmakoterapie   chemicky indukované   MeSH
• psychiatrické posuzovací škály MeSH
• úzkost farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antidepresiva * MeSH

OBJECTIVES: Real-world evidence is needed to inform treatment strategies for patients with PsA and axial SpA (axSpA) who have non-musculoskeletal manifestations (NMMs), various risk factors and comorbidities. International collaboration is required to ensure statistical power and to enhance generalizability. The first step forward is identifying which data are currently being collected. Across 17 registries participating in the European Spondyloarthritis Research Collaboration (EuroSpA), we aimed to map recording practices for NMMs, comorbidities and safety outcomes in patients with PsA and axSpA. METHODS: Through a survey with 4,420 questionnaire items, we explored the recording practices of 58 pre-defined conditions (i.e. NMMs, comorbidities and safety outcomes) covering 10 disease areas. In all registries we mapped for each condition whether it was recorded, the recording procedure and the potential to identify it through linkage to other national registries. RESULTS: Conditions were generally recorded at entry into the registry and clinical follow-up visits using a pre-specified list or a coding system. Most registries recorded conditions within the following disease areas: NMMs (number of registries, n = 15-16), cardiovascular diseases (n = 10-14), gastrointestinal diseases (n = 12-13), infections (n = 10-13) and death (n = 14). Nordic countries had the potential for data linkage and generally had limited recording of conditions in their registry, while other countries had comprehensive recording practices. CONCLUSION: A wide range of conditions were consistently recorded across the registries. The recording practices of many conditions and disease areas were comparable across the registries. Our findings support the potential for future collaborative research.

• Klíčová slova
• DMARDs, JAK inhibitors, biological therapies, comorbidity, multimorbidity, routinely collected data, spondyloarthritis,
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Prenatal mental health problems are associated with morbidity for the pregnant person, and their infants are at long-term risk for poor health outcomes. We aim to explore how the SARS-CoV-2 pandemic affected the mental health of pregnant people in the United Kingdom (UK), and to further identify resilience factors which may have contributed to varying mental health outcomes. We also aim to examine the quality of antenatal care provided during the pandemic in the UK and to identify potential inadequacies to enhance preparedness for future events. METHODS: During June-November 2020, we recruited 3666 individuals in the UK for the EPPOCH pregnancy cohort (Maternal mental health during the COVID-19 pandemic: Effect of the Pandemic on Pregnancy Outcomes and Childhood Health). Participants were assessed for depression, anxiety, anger and pregnancy-related anxiety using validated scales. Additionally, physical activity, social support, individualized support and personal coping ability of the respondents were assessed as potential resilience factors. RESULTS: Participants reported high levels of depression (57.05%), anxiety (58.04%) and anger (58.05%). Higher levels of social and individualized support and personal coping ability were associated with lower mental health challenges. Additionally, pregnant individuals in the UK experienced higher depression during the pandemic than that reported in Canada. Finally, qualitative analysis revealed that restrictions for partners and support persons during medical appointments as well as poor public health communication led to increased mental health adversities and hindered ability to make medical decisions. DISCUSSION: This study revealed increased mental health challenges among pregnant individuals in the UK during the SARS-CoV-2 pandemic. These results highlight the need for reassessing the mental health support measures available to pregnant people in the UK, both during times of crisis and in general.

• Klíčová slova
• anxiety, depression, maternal mental health, mixed methods, pregnancy, resilience, social support,
• Publikační typ
• časopisecké články MeSH

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies, generalized and focal epilepsies, while most other gene discoveries are subtype-specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single nucleotide/short indel-, copy number-, and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies.

• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

BACKGROUND: Long-term deterioration in the mental health of healthcare workers (HCWs) has been reported during and after the COVID-19 pandemic. Determining the impact of COVID-19 incidence and mortality rates on the mental health of HCWs is essential to prepare for potential new pandemics. This study aimed to investigate the association of COVID-19 incidence and mortality rates with depressive symptoms over 2 years among HCWs in 20 countries during and after the COVID-19 pandemic. METHODS: This was a multi-country serial cross-sectional study using data from the first and second survey waves of the COVID-19 HEalth caRe wOrkErS (HEROES) global study. The HEROES study prospectively collected data from HCWs at various health facilities. The target population included HCWs with both clinical and non-clinical roles. In most countries, healthcare centers were recruited based on convenience sampling. As an independent variable, daily COVID-19 incidence and mortality rates were calculated using confirmed cases and deaths reported by Johns Hopkins University. These rates represent the average for the 7 days preceding the participants' response date. The primary outcome was depressive symptoms, assessed by the Patient Health Questionnaire-9. A multilevel linear mixed model (LMM) was conducted to investigate the association of depressive symptoms with the average incidence and mortality rates. RESULTS: A total of 32,223 responses from the participants who responded to all measures used in this study on either the first or second survey, and on both the first and second surveys in 20 countries were included in the analysis. The mean age was 40.1 (SD = 11.1), and 23,619 responses (73.3%) were from females. The 9323 responses (28.9%) were nurses and 9119 (28.3%) were physicians. LMM showed that the incidence rate was significantly and positively associated with depressive symptoms (coefficient = 0.008, standard error 0.003, p = 0.003). The mortality rate was significantly and positively associated with depressive symptoms (coefficient = 0.049, se = 0.020, p = 0.017). CONCLUSIONS: This is the first study to show an association between COVID-19 incidence and mortality rates with depressive symptoms among HCWs during the first 2 years of the outbreak in multiple countries. This study's findings indicate that additional mental health support for HCWs was needed when the COVID-19 incidence and mortality rates increase during and after the early phase of the pandemic, and these findings may apply to future pandemics. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04352634.

• Klíčová slova
• COVID-19, Depressive symptoms, Healthcare worker, Incidence rate, Mortality rate, Multi-country study, Serial cross-sectional study,
• MeSH
• COVID-19 * mortalita   epidemiologie   psychologie   MeSH
• deprese * epidemiologie   MeSH
• dospělí MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• průřezové studie MeSH
• SARS-CoV-2 MeSH
• zdravotnický personál * psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Respiratory pathogens are frequently isolated from airway samples in primary ciliary dyskinesia (PCD) patients. Few studies have investigated associations between these pathogens and lung function, with current management based on evidence from cystic fibrosis. We investigated the association between commonly isolated respiratory pathogens and lung function in PCD patients. METHODS: Using a cross-sectional design, we prospectively collected clinical and concurrent microbiology data from 408 participants with probable or confirmed PCD, aged ≥5 years, from 12 countries. We used Global Lung Function Initiative 2012 references to calculate forced expiratory volume in 1 s (FEV1) z-scores. For 351 patients (86%) with complete data, we assessed the association of the four most frequently isolated pathogens with lung function by fitting multilevel linear models with country as random intercept, adjusted for age at diagnosis, age at lung function, use of antibiotic prophylaxis and body mass index z-scores. RESULTS: Individuals with Pseudomonas aeruginosa growth in culture had significantly lower FEV1 z-scores (β= -0.87, 95% CI -1.40- -0.34), adjusted for presence of Haemophilus influenzae, methicillin-sensitive Staphylococcus aureus and Streptococcus pneumoniae, and for covariates. When stratified by age, associations remained strong for adults but not for children. Results were similar when ciliary defects by transmission electron microscopy were included in the models and when restricting analysis to only confirmed PCD cases. CONCLUSIONS: We found that P. aeruginosa was associated with worse lung function in individuals with PCD, particularly adults. These findings suggest that it is prudent to aim for P. aeruginosa eradication in the first instance, and to treat exacerbations promptly in colonised patients.

• Publikační typ
• časopisecké články MeSH

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause. Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

• Klíčová slova
• Children, Crohn’s disease, Exclusive enteral nutrition, Ustekinumab, wPCDAI,
• MeSH
• Crohnova nemoc * farmakoterapie   MeSH
• dítě MeSH
• indukce remise MeSH
• lidé MeSH
• mladiství MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci MeSH
• ustekinumab * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• ustekinumab * MeSH

BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

• Klíčová slova
• adherence, adverse effects, bismuth, dyspepsia, effectiveness, efficacy, first line, rate, regimens, rescue,
• MeSH
• amoxicilin * terapeutické užití   aplikace a dávkování   MeSH
• antibakteriální látky * terapeutické užití   škodlivé účinky   MeSH
• bismut terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• dyspepsie farmakoterapie   mikrobiologie   MeSH
• Helicobacter pylori * účinky léků   MeSH
• infekce vyvolané Helicobacter pylori * farmakoterapie   MeSH
• inhibitory protonové pumpy * terapeutické užití   aplikace a dávkování   MeSH
• klarithromycin terapeutické užití   MeSH
• kombinovaná farmakoterapie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• metronidazol terapeutické užití   aplikace a dávkování   MeSH
• prospektivní studie MeSH
• registrace * 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
• Geografické názvy
• Evropa MeSH
• Názvy látek
• amoxicilin * MeSH
• antibakteriální látky * MeSH
• bismut MeSH
• inhibitory protonové pumpy * MeSH
• klarithromycin MeSH
• metronidazol MeSH