Primary ciliary dyskinesia (PCD) is a genetic disorder associated with recurrent and chronic respiratory infections due to functional defects of motile cilia. In this study, we aimed to elucidate inflammatory and proliferative responses in PCD respiratory epithelium and evaluate the effect of Azithromycin (AZT) on these responses. Airway basal cells (BCs) were isolated from nasal samples of Wild-type (WT) epitope of healthy donors and PCD donors with bi-allelic mutations in DNAH5, DNAH11 and CCDC39. Cells were expanded in vitro and stimulated with either Lipopolysaccharide (LPS) or vehicle control. Post stimulation, cells were treated with either Azithromycin (AZT) or vehicle control. Cell proliferation was imaged in real-time. Separately, BCs from the same donors were expanded and grown at an air-liquid interface (ALI) to generate a multi-ciliated epithelium (MCE). Once fully mature, cells were stimulated with LPS, AZT, LPS + AZT or vehicle control. Inflammatory profiling was performed on collected media by cytokine Luminex assay. At baseline, there was a significantly higher mean production of pro-inflammatory cytokines by CCDC39 BCs and MCEs when compared to WT, DNAH11 and DNAH5 cells. AZT inhibited production of cytokines induced by LPS in PCD cells. Differences in cell proliferation were noted in PCD and this was also corrected with AZT treatment.
AIM: To investigate the epidemiology of Clostridioides difficile infection (CDI) in Slovakian hospitals after the emergence of ribotype 176 (027-like) in 2016. METHODS: Between 2018 and 2019, European Centre for Disease Control and Prevention CDI surveillance protocol v2.3 was applied to 14 hospitals, with additional data collected on recent antimicrobial use and the characterization of C. difficile isolates. RESULTS: The mean hospital incidence of CDI was 4.1 cases per 10,000 patient bed-days. One hundred and five (27.6%) in-hospital deaths were reported among the 381 cases. Antimicrobial treatment within the previous 4 weeks was recorded in 90.5% (333/368) of cases. Ribotype (RT)176 was detected in 50% (n=185/370, 14 hospitals) and RT001 was detected in 34.6% (n=128/370,13/14 hospitals) of cases with RT data. Overall, 86% (n=318/370) of isolates were resistant to moxifloxacin by Thr82Ile in GyrA (99.7%). Multi-locus variable tandem repeat analysis showed clonal relatedness of predominant RTs within and between hospitals. Seven of 14 sequenced RT176 isolates and five of 13 RT001 isolates showed between zero and three allelic differences by whole-genome multi-locus sequence typing. The majority of sequenced isolates (24/27) carried the erm(B) gene and 16/27 also carried the aac(6')-aph(2'') gene with the corresponding antimicrobial susceptibility phenotypes. Nine RT176 strains carried the cfr(E)gene and one RT001 strain carried the cfr(C) gene, but without linezolid resistance. CONCLUSIONS: The newly-predominant RT176 and endemic RT001 are driving the epidemiology of CDI in Slovakia. In addition to fluoroquinolones, the use of macrolide-lincosamide-streptogramin B antibiotics can represent another driving force for the spread of these epidemic lineages. In C. difficile, linezolid resistance should be confirmed phenotypically in strains with detected cfr gene(s).
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- Clostridioides difficile * genetika MeSH
- Clostridioides genetika MeSH
- fluorochinolony farmakologie MeSH
- klostridiové infekce * epidemiologie farmakoterapie MeSH
- lidé MeSH
- linezolid MeSH
- makrolidy MeSH
- mikrobiální testy citlivosti MeSH
- multilokusová sekvenční typizace MeSH
- ribotypizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
BACKGROUND: The growing number of patients with type 2 diabetes and prediabetes is a major public health concern. Physical activity is a cornerstone of diabetes management and may prevent its onset in prediabetes patients. Despite this, many patients with (pre)diabetes remain physically inactive. Primary care physicians are well-situated to deliver interventions to increase their patients' physical activity levels. However, effective and sustainable physical activity interventions for (pre)diabetes patients that can be translated into routine primary care are lacking. METHODS: We describe the rationale and protocol for a 12-month pragmatic, multicentre, randomised, controlled trial assessing the effectiveness of an mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED). Twenty-one general practices will recruit 340 patients with (pre)diabetes during routine health check-ups. Patients allocated to the active control arm will receive a Fitbit activity tracker to self-monitor their daily steps and try to achieve the recommended step goal. Patients allocated to the intervention arm will additionally receive the mHealth intervention, including the delivery of several text messages per week, with some of them delivered just in time, based on data continuously collected by the Fitbit tracker. The trial consists of two phases, each lasting six months: the lead-in phase, when the mHealth intervention will be supported with human phone counselling, and the maintenance phase, when the intervention will be fully automated. The primary outcome, average ambulatory activity (steps/day) measured by a wrist-worn accelerometer, will be assessed at the end of the maintenance phase at 12 months. DISCUSSION: The trial has several strengths, such as the choice of active control to isolate the net effect of the intervention beyond simple self-monitoring with an activity tracker, broad eligibility criteria allowing for the inclusion of patients without a smartphone, procedures to minimise selection bias, and involvement of a relatively large number of general practices. These design choices contribute to the trial's pragmatic character and ensure that the intervention, if effective, can be translated into routine primary care practice, allowing important public health benefits. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05351359, 28/04/2022).
- MeSH
- cvičení MeSH
- diabetes mellitus 2. typu * prevence a kontrola MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- pragmatické klinické studie jako téma MeSH
- praktické lékařství * MeSH
- prediabetes * terapie MeSH
- randomizované kontrolované studie jako téma MeSH
- sedavý životní styl MeSH
- telemedicína * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- protokol klinické studie MeSH
BACKGROUND: Children of parents with a mental illness are at high risk of developing a mental disorder as a result of transgenerational transmission. Without effective intervention, they could form the next generation of psychiatric patients. ChildTalks+ is a preventive intervention involving four structured psychoeducational sessions designed for parents affected by a mental disorder and their children. Its aim is to reduce the risk of mental disorders in children of parents with mental illness. This study draws on our clinical practice and involves a group of patients with eating disorders. The aim of the project, which will run in the Czech Republic, is to evaluate the effectiveness of ChildTalks+ methodology. METHODS: ChildTalks+ therapists (professionals from health, social, and educational facilities) will recruit 66 families where a parent is treated for a mental disorder and the family includes children aged 6-18. Paired allocation into an intervention group (N = 33) and a control group (N = 33) will be based on the number of risk factors identified in the family. Both groups will complete questionnaires at the baseline, post-test, and follow-up assessments after six and 12 months. The intervention group will receive the ChildTalks+ intervention within 2 months of the baseline assessment; the control group after the last assessment. Questionnaires will be completed by parents and children aged 12+ and, in two cases, 15+ years. Quantitative data will be supplemented with qualitative data from ChildTalks+ therapists working with patients with eating disorders. DISCUSSION: The ChildTalks+ intervention is expected to strengthen parenting competencies and family protective factors, improve family communication, increase awareness of parental mental health issues, and improve the wellbeing of children of parents with mental illness with long-term sustainable outcomes. The study should contribute to the evidence base for the ChildTalks+ program and help identify key themes in the implementation of similar preventive interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05554458. Registered 26 September 2022. Retrospectively registered.
- MeSH
- dítě MeSH
- klinické zkoušky kontrolované jako téma MeSH
- lidé MeSH
- poruchy příjmu potravy * prevence a kontrola MeSH
- průzkumy a dotazníky MeSH
- rodiče * psychologie MeSH
- rodičovství psychologie MeSH
- výzkumný projekt MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- protokol klinické studie MeSH
INTRODUCTION: Tinnitus is an intrusive and chronic illness affecting a significant portion of the population, decreasing affected individuals' quality of life and socioeconomic functioning. Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulatory method utilizing weak electrical currents to elicit short and long-term central nervous system changes. Several studies have proven its effect on tinnitus. We aimed to broaden the knowledge and provide data on the effect and its retention. METHODS: In the randomized, double-blinded, sham-controlled trial, 39 patients (active n = 19, sham n = 20) underwent bifrontal tDCS (anode over right dorsolateral prefrontal cortex (DLPFC), cathode left DLPFC, current of 1.5 mA, 20 min, 6 sessions in 2 weeks). Tinnitus Functional Index (TFI), Iowa Tinnitus Handicap Questionnaire (ITHQ), Beck Anxiety Inventory (BAI), Zung Self-Rating Depression Scale (SDS), and WHO-Quality of Life-BREF were employed in 4 evaluation points, including the follow-ups of 6 weeks and 6 months. RESULTS: We reached a delayed, significant long-term improvement (p < 0.05) in auditory difficulties associated with tinnitus and noticed it even after 6 months compared to placebo. We also reached a short-term, negative effect in the psychological domain of WHO-Quality of Life-BREF (p < 0.05). Not all subdomains of TFI and ITHQ reached statistical significance during the data analysis, even though specific positive trends were noticed. CONCLUSION: We proved partial, positive, long-term effects of tDCS on tinnitus and short-term, negative, transient effect on a specific aspect of the general quality of life. We expanded upon the results of previous trials and provided data concerning the longevity and the precise effect of multiple sessions, bifrontal DLPFC tDCS. Our sample size (n = 39) was limited, which might have contributed to the lesser statistical power of the analyzed items. CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier [NCT05437185].
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Electrophysiological diagnosis of cardiac autonomic neuropathy (CAN) is based on the evaluation of cardiovascular autonomic reflex tests (CARTs). CARTs are relatively time consuming and must be performed under standardized conditions. This study aimed to determine whether thermal quantitative sensory testing (TQST) can be used as a screening tool to identify patients with diabetes at a higher risk of CAN. METHODS: Eighty-five patients with diabetes and 49 healthy controls were included in the study. Neurological examination, CARTs, TQST, biochemical analyses, and neuropathy symptom questionnaires were performed. RESULTS: CAN was diagnosed in 46 patients with diabetes (54%). CAN-positive patients with diabetes had significantly higher warm detection thresholds (WDT) and significantly lower cold detection thresholds (CDT) in all tested regions (thenar, tibia, and the dorsum of the foot). CDT on the dorsum < 21.8°C in combination with CDT on the tibia < 23.15°C showed the best diagnostic ability in CAN prediction, with 97.4 % specificity, 60.9% sensitivity, 96.6% positive predictive value, and 67.3% negative predictive value. CONCLUSION: TQST can be used as a screening tool for CAN before CART.
- MeSH
- autonomní nervový systém MeSH
- diabetes mellitus * MeSH
- diabetické neuropatie * diagnóza MeSH
- lidé MeSH
- nemoci nervového systému * MeSH
- nemoci periferního nervového systému * diagnóza MeSH
- senzorické prahy fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND AND PURPOSE: The effect of pregnancy on brain changes and radiological disease activity in women with multiple sclerosis (MS) is not well understood. This study was undertaken to describe the dynamics of lesion activity and brain volume changes during the pregnancy and postpartum periods. METHODS: This observational study of 62 women with relapsing-remitting MS included magnetic resonance imaging (221 scans) as well as clinical visits at baseline (<24 and >6 months before pregnancy), prepregnancy (<6 months before pregnancy), postpartum (<3 months after delivery), and follow-up (>12 and <24 months after delivery) periods. RESULTS: The majority of women had a mild disability and a short disease duration (median = 5.5 years). Eighteen (29.0%) women had a relapse during the year preceding pregnancy onset, nine (14.5%) during pregnancy, and 20 (32.3%) in the year following delivery. Disability status remained unchanged during follow-up. Women in the postpartum period (n = 62) had higher T2 lesion volume (median = 1.18 ml vs. 0.94 ml), greater annualized T2 lesion volume increase (0.23 ml vs. 0.0 ml), lower brain parenchymal fraction (85.6% vs. 86.4%), and greater annualized brain volume loss (-1.74% vs. -0.16%) compared with the prepregnancy period (all p < 0.001). At 12-24 months after delivery, women (n = 41) had higher T2 lesion volume (1.16 ml vs. 1.0 ml) and lower brain parenchymal fraction (86.0% vs. 86.5%) compared to the prepregnancy period (both p < 0.001). CONCLUSIONS: The postpartum period was associated with an increase in T2 lesion volume and accelerated brain volume loss in a considerable proportion of women. This should be considered in treatment decision-making and designing clinical trials.
- MeSH
- atrofie patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozek diagnostické zobrazování patologie MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie MeSH
- roztroušená skleróza * diagnostické zobrazování patologie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
PURPOSE: We aimed to evaluate the efficacy of different antibiotic regimens for the treatment of Clostridioides difficile infection (CDI) with regard to the CDI episode number and disease severity. METHODS: An observation cohort study included 271 CDI patients hospitalised between 2013-2016. Univariate logistic regression was used to evaluate the association between patients' clinical outcome (sustained clinical cure or recurrence) in a 60-day follow-up and the antibiotic regimen used (oral metronidazole, oral vancomycin, combination of oral vancomycin and metronidazole, oral fidaxomicin). Subgroup analyses, based on CDI episode number and severity, were performed. RESULTS: In the overall population, fidaxomicin was superior to metronidazole, vancomycin or their combination, for a sustained clinical response and in the prevention of recurrent CDI (rCDI). In the subgroup analyses, fidaxomicin was superior to vancomycin or metronidazole for a sustained clinical response and in the prevention of rCDI in the initial episode, first recurrence and non-severe cases. In the oral treatment of severe CDI, fidaxomicin had a similar treatment outcome to vancomycin and none of the antibiotic treatments were superior in the prevention of rCDI. Fidaxomicin, vancomycin, or a combination of metronidazole and vancomycin, had similar outcomes for sustained clinical response and prevention of rCDI in patients with multiple rCDI. CONCLUSION: Fidaxomicin was superior to metronidazole or vancomycin for the treatment of the initial episode, first recurrence, and non-severe CDI.
- MeSH
- antibakteriální látky farmakologie MeSH
- aplikace orální MeSH
- Clostridioides difficile účinky léků MeSH
- fidaxomicin farmakologie MeSH
- hospitalizace MeSH
- klostridiové infekce farmakoterapie mikrobiologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- logistické modely MeSH
- metronidazol farmakologie MeSH
- recidiva MeSH
- senioři MeSH
- vankomycin farmakologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
The objective of this study was to compare semen quality (sperm density, progressive motility and spermia) between long-term childhood cancer survivors and a control group of males. The second objective was to correlate the semen analysis of the survivors with cancer treatment and endocrine status. The semen quality of 143 survivors (median age, 23.6 years) was compared to 200 men (median age, 27.9 years) who had not been diagnosed with cancer. The cancer-related risk factors and gonadotrophin levels were compared. Overall, 65% of the survivors had abnormal semen analysis compared to 26.5% of the controls (p < 0.0001). Survivors with nonaspermia had lower sperm density than the controls (p < 0.001). Other observed correlations were not significant. Survivors who were treated with alkylating agents were more likely to have abnormal semen analysis (p < 0.008). Follicle-stimulating hormone and luteinising hormone levels were significantly elevated (p < 0.0001) in survivors with abnormal semen analysis. The semen quality parameters, except for low sperm density, did not differ in survivors with nonaspermia compared to the controls. The risk factors included treatment with alkylating agents. Elevated gonadotrophin levels correlated with abnormal semen analysis. All cancer survivors should be made aware of the possibility of suffering from cancer treatment-related infertility.
- MeSH
- analýza spermatu MeSH
- dítě MeSH
- dospělí MeSH
- folikuly stimulující hormon MeSH
- lidé MeSH
- mladý dospělý MeSH
- motilita spermií MeSH
- mužská infertilita * etiologie MeSH
- nádory * farmakoterapie MeSH
- počet spermií MeSH
- přežívající onkologičtí pacienti * MeSH
- přežívající MeSH
- rizikové faktory MeSH
- sperma MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: With the increasing number of detected lung nodules and the need for morphological verification, the number of CT- controlled biopsies is increasing. The aim of this study was to assess the risks and benefits of these biopsies. METHODS: This is a prospective and observational study. We evaluated 101 punctures performed on a group of 90 consecutive patients in the Department of Radiology. RESULTS: In patients with a mean age of 66 years, with mostly accidentally detected lung nodules, we observed complications 38 times. The most common were minor pneumothoraxes or insignificant bleedings. In 6 patients, the complications were more serious, 5 times the pneumothoraxes required chest drainage, once massive hemoptysis was recorded. The lesions were successfully biopsied 78 times, the target was missed 23 times. The diagnosis of lung cancer (LC) was confirmed in 60 patients, 49 LCs were verified by puncture under CT control. 42% (25/60) of patients with LC were diagnosed in TNM stages I and II. 23% (14/60) of patients with LC were treated surgically. The remaining 30 patients most often suffered from lung metastazes (13/30), in 8 of them an inflammatory lung disease was diagnosed. 69 patients underwent bronchoscopy, in only 19% (13/69) it contributed to the diagnosis. In a model "screening like" group of 49 patients with only randomly detected lung deposits, we diagnosed LC in 76% (37/49). 49% (18/37) were in TNM stage I and II, 11 were treated surgically. CONCLUSIONS: CT-controlled biopsy of lung lesions is an effective and safe diagnostic method.
