BACKGROUND: Congenital myasthenic syndromes (CMSs) are characterized by hypotonia, episodic apnea, muscle weakness, ptosis and generalized fatigability. CMS type 20 (CMS20) is a rare disorder caused by variants in SLC5A7. In contrast to most other CMSs, CMS20 is also associated with neurodevelopmental disorders (NDDs). Only 19 patients from 14 families have been reported so far. METHODS: We studied a 12-year-old boy with symptoms manifested at six weeks of age. Later, he also showed speech delay, moderate intellectual disability and autism. Analysis of CMS genes known at the time of clinical diagnosis yielded no results. Trio exome sequencing (ES) was performed. RESULTS: ES revealed compound heterozygosity for two SLC5A7 variants, p.(Asn431Lys) and p.(Ile291Thr). While the first variant was absent from all databases, the second variant has already been described in one patient. In silico analysis of known pathogenic SLC5A7 variants showed that variants with a higher predicted deleteriousness may be associated with earlier onset and increased severity of neuromuscular manifestations. CONCLUSION: Our patient confirms that CMS20 can be associated with NDDs. The study illustrates the strength of ES in deciphering the genetic basis of rare diseases, contributes to characterization of CMS20 and suggests trends in genotype-phenotype correlation in CMS20.
- MeSH
- genetické asociační studie MeSH
- heterozygot MeSH
- kongenitální myastenické syndromy * genetika diagnóza MeSH
- lidé MeSH
- mentální retardace * komplikace MeSH
- missense mutace MeSH
- symportéry * genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
BACKGROUND: Positive findings on early detection and early intervention services have been consistently reported from many different countries. The aim of this study, conducted within the European Brain Council project "The Value of Treatment", was to estimate costs and the potential cost- savings associated with adopting these services within the context of the Czech mental health care reform. METHODS: Czech epidemiological data, probabilities derived from meta-analyses, and data on costs of mental health services in the Czech Republic were used to populate a decision analytical model. From the health care and societal perspectives, costs associated with health care services and productivity lost were taken into account. One-way sensitivity analyses were conducted to explore the uncertainty around the key parameters. RESULTS: It was estimated that annual costs associated with care as usual for people with the first episode of psychosis were as high as 46 million Euro in the Czech Republic 2016. These annual costs could be reduced by 25% if ED services were adopted, 33% if EI services were adopted, and 40% if both, ED and EI services, were adopted in the country. Cost-savings would be generated due to decreased hospitalisations and better employment outcomes in people with psychoses. CONCLUSIONS: Adopting early detection and early intervention services in mental health systems based on psychiatric hospitals and with limited access to acute and community care could generate considerable cost- savings. Although the results of this modelling study needs to be taken with caution, early detection and early intervention services are recommended for multi-centre pilot testing accompanied by full economic evaluation in the region of Central and Eastern Europe.
- MeSH
- analýza nákladů a výnosů MeSH
- časná diagnóza MeSH
- hospitalizace ekonomika MeSH
- lidé MeSH
- metody pro podporu rozhodování MeSH
- náklady na zdravotní péči * MeSH
- psychotické poruchy diagnóza MeSH
- schizofrenie diagnóza MeSH
- služby péče o duševní zdraví ekonomika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
OBJECTIVES: Suboptimal medication adherence is common among patients with hypertension. Measurements of plasma or urinary levels of antihypertensive drugs are useful, but not widely available. The aim of our study was to investigate the relation of patients' heart rates to their serum beta-blocker levels. METHODS: We correlated 220 measurements of serum beta-blocker levels in 106 patients with apparently resistant hypertension to their corresponding office heart rate. A significant proportion, 44.6% of patients, were non-adherent to beta-blocker treatment according to serum level measurement. Non-adherent patients had significantly higher heart rates (80.9 vs. 66.6 bpm, p < .001), systolic (157.4 vs. 147.0 mm Hg, p = .002) and diastolic blood pressure (91.1 vs. 87.2 mm Hg, p = .041) in comparison to adherent patients. RESULTS: Heart rate above 75.5 beats per minute predicted non-adherence to beta-blocker treatment with a sensitivity of 62.5%, specificity 86.8% and AUC ROC 0.802 (p < .001). Higher heart rate cutoff might be applicable for nebivolol but was not determined due to the low number of patients treated with nebivolol. CONCLUSIONS: We concluded that heart rate was shown to be a good predictor of non-adherence to beta-blocker treatment, and might become a quick and easy measure to determine patient adherence in hypertensive patients.
- MeSH
- beta blokátory krev terapeutické užití MeSH
- hypertenze farmakoterapie patofyziologie MeSH
- krevní tlak účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- monitorování léčiv MeSH
- nebivolol krev terapeutické užití MeSH
- retrospektivní studie MeSH
- srdeční frekvence účinky léků MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The purpose of this study was to determine the relation between posturally increased intra-abdominal pressure and lower/upper esophageal sphincter pressure changes in patients with gastroesophageal reflux disease. We used high resolution manometry to measure pressure changes in lower and upper esophageal sphincter during bilateral leg rise. We also examined whether the rate of lower and upper esophageal sphincter pressure would increase during leg raise differentially in individuals with versus without normal resting pressure. Fifty eight patients with gastroesophageal reflux disease participated in the study. High resolution manometry was performed in relaxed supine position, then lower and upper esophageal sphincter pressure was measured. Finally, the subjects were instructed to keep their legs lifted while performing 90-degree flexion at the hips and knees and the pressure was measured again. Paired t-test and independent samples t-test were used. There was a significant increase in both lower (P < 0.001) and upper esophageal sphincter pressure (P = 0.034) during leg raise compared to the initial resting position. Individuals with initially higher pressure in lower esophageal sphincter (>10 mmHg) exhibited a greater pressure increase during leg raise than those with initially lower pressure (pressure ≤10 mmHg; P = 0.002). Similarly individuals with higher resting upper esophageal sphincter pressure (>44 mmHg) showed a greater pressure increase during leg raise than those with lower resting pressure (≤44 mmHg; P < 0.001). The results illustrate the influence of postural leg activities on intraesophageal pressure in patients with gastroesophageal reflux disease, indicating by means of high resolution manometry that diaphragmatic postural and sphincter function are likely interrelated in this population.
- MeSH
- bérec fyziologie MeSH
- dolní jícnový svěrač fyziologie MeSH
- dospělí MeSH
- gastroezofageální reflux patofyziologie MeSH
- horní jícnový svěrač fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- manometrie MeSH
- postura těla MeSH
- senioři MeSH
- svalová kontrakce fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) are two distinct clinically overlapping syndromes caused by de novo heterozygous truncating mutations in the KAT6B gene encoding lysine acetyltransferase 6B, a part of the histone H3 acetyltransferase complex. We describe an 8-year-old girl with a KAT6B mutation and a combined GPS/SBBYSS phenotype. The comparison of this patient with 61 previously published cases with KAT6B mutations and GPS, SBBYSS or combined GPS/SBBYSS phenotypes allowed us to separate the KAT6B mutations into four groups according to their position in the gene (reflecting nonsense mediated RNA decay and protein domains) and their clinical outcome. We suggest that mutations in mid-exon 18 corresponding to the C-terminal end of the acidic (Asp/Glu-rich) domain of KAT6B may have more variable expressivity leading to GPS, SBBYSS or combined phenotypes, in contrast to defects in other regions of the gene which contribute more specifically to either GPS or SBBYSS. Notwithstanding the clinical overlap, our cluster analysis of phenotypes of all known patients with KAT6B mutations supports the existence of two clinical entities, GPS and SBBYSS, as poles within the KAT6B-related disease spectrum. The awareness of these phenomena is important for qualified genetic counselling of patients with KAT6B mutations.
- MeSH
- blefarofimóza diagnóza genetika MeSH
- dítě MeSH
- exony * MeSH
- faciální stigmatizace MeSH
- fenotyp MeSH
- histonacetyltransferasy genetika MeSH
- kongenitální hypotyreóza diagnóza genetika MeSH
- kraniofaciální abnormality diagnóza genetika MeSH
- ledviny abnormality MeSH
- lidé MeSH
- mentální retardace diagnóza genetika MeSH
- molekulární sekvence - údaje MeSH
- mutace * MeSH
- nestabilita kloubu diagnóza genetika MeSH
- patela abnormality MeSH
- psychomotorické poruchy diagnóza genetika MeSH
- sekvence nukleotidů MeSH
- skrotum abnormality MeSH
- urogenitální abnormality diagnóza genetika MeSH
- vrozené srdeční vady diagnóza genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Besides main disease symptoms, disturbing dreams are often found in narcoleptics and may contribute to disturbed sleep. Our main goal was to study different types of oneiric activity in narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (N). METHODS: We have analyzed the medical history of 118 narcoleptics (64 men, 86 with NC, 32 with N, mean age 41.6±15 years). Their most frequent dreams were divided into four groups: (A) low recall/mundane dreams, (B) vivid dreams without disturbing negative emotion, (C) nightmares, (D) reduction of nightmares, possibly by medication. Associations with other features of the disease were statistically analyzed. RESULTS: Nightmares were found in one-third of the patients, proportionally distributed in N and NC groups; not negatively charged vivid dreams appeared more frequently in NC patients (P<0.005). No/mundane dreams occurred with higher prevalence in men (48%) than in women (20%), (P<0.005), without any significant influence of age. Occurrence of nightmares was significantly higher in patients with REM sleep behavior (P<0.05), but lower in patients with obstructive sleep apnea (P<0.005). Polysomnographic correlation of N and NC nightmare groups showed more wakefulness (P<0.05) and higher percentage of NREM1 stage (P<0.05) in NC patients with nightmares. CONCLUSION: Compared with the general population, nightmares seem to be significantly more prevalent in both NC and N, and they are not sufficiently investigated and treated. The neurobiological basis of narcolepsy and patients' dreaming activities appear to be closely related.
