Effects of bone and mineral metabolism on arterial elasticity in chronic renal failure

Arterial stiffness (Ast) individually predicts cardiovascular (CV) mortality. Ast increases via vascular calcification and can be characterized by pulse wave velocity (PWV). We assessed the influence of mineral and bone metabolism on Ast in dialyzed (D) and renal transplanted (Tx) children by measuring fetuin-A and bone markers [bone-specific alkaline phosphatase (BALP); beta-CrossLaps (β)]. Normalized PWV/height (PWV/h) of 11 D and 17 Tx patients was measured by applanation tonometry. Levels of calcium (Ca), phosphate (P), fetuin-A, and bone markers were analyzed. Ca × P/fetuin-A ratio was calculated to characterize the balance of calcification and inhibition. Cumulative dose of calcitriol was also assessed. Fetuin-A was lower in D and Tx compared with healthy controls. Bone markers and Ca × P/fetuin-A of D were significantly higher than those of Tx and controls. In D PWV/h correlated with Ca × P/fetuin-A and BALP (r = 0.8; p = 0.005, r = 0.6, p = 0.05, respectively); BALP correlated with Ca × P/fetuin-A (r = 0.7, p = 0.01). In Tx, there was a correlation between calcitriol administered before transplantation and PWV/h (r = 0.5, p = 0.04). Increased bone turnover was coupled with an increased potential of calcium-phosphate precipitation, as shown by the increased Ca × P/fetuin-A. It might explain the connection between disturbed mineral and bone metabolism and Ast. Tx might be beneficial on Ast, though follow-up studies are needed.     

RAR beta2 suppression in head and neck squamous cell carcinoma correlates with site, histology and age

Retinoids as important growth and differentiation regulating agents have a potential role in the chemoprevention of head and neck squamous cell carcinoma (HNSCC). Despite the promising preclinical and early clinical findings, limitations of application are raised by intrinsic resistance acquired during carcinogenesis. Retinoic acid receptor beta2 (RAR beta2) is one of the proximate mediators of retinoid signalling and its expression is often diminished in early stages of head and neck carcinogenesis. One form of retinoid resistance has been associated with the methylation-induced silencing of the RAR beta gene. We studied primary HNSCC samples of different anatomical sites in respect of methylation, expression and allelic loss of RAR beta gene. A strong correlation (p<0.01) was found between hyper-methylation and reduced expression of RAR beta2, however the allelic loss at 3p24, the locus of RAR beta, did not considerably influence its mRNA level. Hypopharynx tumors showed significantly lower hypermethylation (p<0.05) and higher mRNA expression levels of RAR beta2 compared to the tumors located at other sites of the head and neck. We could also provide evidence that poorly differentiated grade 3 tumors had significantly higher RAR beta2 expression and lower methylation levels (p<0.05) than better differentiated grade 1 and grade 2 tumors. In addition, we found a good correlation between the methylation degree of the RAR beta2 promoter and the ages of patients. Collectively, our results suggest that evaluation of several factors such as tumor location, age, histology and methylation state of the RAR beta gene might contribute to the selection of patients for retinoid-based chemoprevention.     

The burden of type 2 diabetes mellitus in states of the European Union and United Kingdom at the national and subnational levels: A systematic review

Type 2 diabetes mellitus (T2D) is a highly prevalent disease worldwide, with an equally increased expenditure associated with it. We aimed to longitudinally evaluate the epidemiologic and economic burden of T2D in the current member states of the European Union and the United Kingdom (EU-28). The present systematic review is registered on PROSPERO (CRD42020219894), and it followed the PRISMA guidelines. Eligibility criteria comprised original observational studies in English reporting economic and epidemiological data for T2D in member states of the EU-28. Methodological assessment was performed with the Joanna Briggs Institute (JBI) Critical Appraisal Tools. The search retrieved 2253 titles and abstracts. After study selection, 41 studies were included in the epidemiologic analysis and 25 in the economic analysis. Economic and epidemiologic studies covered only 15 member states with reported data between 1970 and 2017, resulting in an incomplete picture. For children in particular, limited information is available. The prevalence, incidence, mortality, and expenditure of the T2D population have increased across the decades in member states. Therefore, policies should aim to prevent or reduce the burden of T2D in the EU and consequently mitigate the expenditure on T2D.     

REM Sleep Microstates in the Human Anterior Thalamus

Rapid eye movement (REM) sleep is an elusive neural state that is associated with a variety of functions from physiological regulatory mechanisms to complex cognitive processing. REM periods consist of the alternation of phasic and tonic REM microstates that differ in spontaneous and evoked neural activity. Although previous studies indicate, that cortical and thalamocortical activity differs across phasic and tonic microstates, the characterization of neural activity, particularly in subcortical structures that are critical in the initiation and maintenance of REM sleep is still limited in humans. Here, we examined electric activity patterns of the anterior nuclei of the thalamus as well as their functional connectivity with scalp EEG recordings during REM microstates and wakefulness in a group of epilepsy patients (N = 12, 7 females). Anterothalamic local field potentials (LFPs) showed increased high-α and β frequency power in tonic compared with phasic REM, emerging as an intermediate state between phasic REM and wakefulness. Moreover, we observed increased thalamocortical synchronization in phasic compared with tonic REM sleep, especially in the slow and fast frequency ranges. Wake-like activity in tonic REM sleep may index the regulation of arousal and vigilance facilitating environmental alertness. On the other hand, increased thalamocortical synchronization may reflect the intrinsic activity of frontolimbic networks supporting emotional and memory processes during phasic REM sleep. In sum, our findings highlight that the heterogeneity of phasic and tonic REM sleep is not limited to cortical activity, but is also manifested by anterothalamic LFPs and thalamocortical synchronization.SIGNIFICANCE STATEMENT REM sleep is a heterogeneous sleep state that features the alternation of two microstates, phasic and tonic rapid eye movement (REM). These states differ in sensory processing, awakening thresholds, and cortical activity. Nevertheless, the characterization of these microstates, particularly in subcortical structures is still limited in humans. We had the unique opportunity to examine electric activity patterns of the anterior nuclei of the thalamus (ANTs) as well as their functional connectivity with scalp EEG recordings during REM microstates and wakefulness. Our findings show that the heterogeneity of phasic and tonic REM sleep is not limited to cortical activity, but is also manifested in the level of the thalamus and thalamocortical networks.     

Vaccine-driven serotype-rearrangement is seen with latency in clinical isolates: Comparison of carried and clinical pneumococcal isolates from the same time period in Hungary

Young children – the main asymptomatic carriers of pneumococcus – are often the source of pneumococcal infections. PCV13 replaced PCV7 in 2010 in Hungary and it became a mandatory vaccine in 2014. In this work we surveyed the effect of vaccination in three groups: in healthy children under 7?years; in children of the same age but infected with pneumococcus (P1); in older patients (P2) who were very likely not vaccinated.Nasal swabs were taken from 522 healthy children to screen pneumococcal carriage between March 2015 and May 2016. In the same time period, 146 clinical isolates were collected, mainly from mucosal infections. Serotypes, antibiotic susceptibility and clonality of the isolates was determined and compared.The carriage rate was 39.1%. Regarding carriage, the serotype distribution showed the total disappearance of serotypes 3 and 6A compared to former Hungarian studies. The prevalence of PCV13 serotypes was only 5.8% represented by three serotypes (19F, 19A, 9V). Of note, serotype 19A (a very resistant and invasive type) also decreased significantly. In the patient groups, PCV13 prevalence was higher: 17.5% (P1) and 32.6% (P2). Although serotype 3 was present in P1 (7.9%), the leading serotype was 23B (22.2%), a non-vaccine type (NVT). P2 showed the most diverse serotype distribution, but serotype 3 was predominant here (15.7%). Pneumococcal isolates from the patients were more resistant towards the tested antibiotics compared to those from carriers.PCV13 seems to be highly successful in reducing the prevalence of vaccine serotypes. The serotype-rearrangement can be seen also among clinical isolates, albeit somewhat later in time. Fortunately, the replacing serotypes are less invasive and less resistant, but, most worrisome, serotype 19F can be found again with increased frequency among carriage isolates and mucosal infections. Further surveillance is needed to carefully monitor such successful, antibiotic resistant “refugees”.     

Cost-of-illness in patients with moderate to severe psoriasis: a cross-sectional survey in Hungarian dermatological centres

Background

Despite the widespread availability of biological drugs in psoriasis, there is a shortage of disease burden studies.

Objectives

To assess the cost-of-illness and quality of life of patients with moderate to severe psoriasis in Hungary.

Methods

Consecutive patients with Psoriasis Area and Severity Index (PASI) > 10 and Dermatology Life Quality Index (DLQI) > 10, or treated with traditional systemic (TST) or biological systemic treatment (BST) were included. Demographic data, clinical characteristics, psoriasis related medication, health care utilizations and employment status in the previous 12 months were recorded. Costing was performed from the societal perspective applying the human capital approach. Quality of life was assessed using DLQI and EQ-5D measures.

Results

Two-hundred patients were involved (females 32 %) with a mean age of 51 (SD 13) years, 103 (52 %) patients were on BST. Mean PASI, DLQI and EQ-5D scores were 8 (SD 10), 6 (SD 7) and 0.69 (SD 0.3), respectively. The mean total cost was €9,254/patient/year (SD 8,502) with direct costs accounting for 86 %. The main cost driver was BST (mean €7,339/patient/year). Total costs differed significantly across treatment subgroups, mean (SD): no systemic therapy €2,186 (4,165), TST €2,388 (4,106) and BST €15,790 (6,016) (p < 0,001). Patients with BST had better PASI and DLQI scores (p < 0.01) than the other two subgroups.

Conclusions

Patients with biological treatment have a significantly better quality of life and higher total costs than patients with or without traditional systemic treatment. Our study is the largest in Europe and the first in the CEE region that provides cost-of-illness data in psoriasis involving patients with BST.

     

Influence of patient characteristics on preventive service delivery and general practitioners’ preventive performance indicators: A study in patients with hypertension or diabetes mellitus from Hungary

Background: Regular primary healthcare (PHC) performance monitoring to produce a set of performance indicators for provider effectiveness is a fundamental method for improving guideline adherence but there are potential negative impacts of the inadequate application of this approach. Since performance indicators can reflect patient characteristics and working environments, as well as PHC team contributions, inadequate monitoring practices can reduce their effectiveness in the prevention of cardiometabolic disorders.

Objectives: To describe the influence of patients’ characteristics on performance indicators of PHC preventive practices in patients with hypertension or diabetes mellitus.

Methods: This cross-sectional analysis was based on a network of 165 collaborating GPs. A random sample of 4320 adults was selected from GP’s patient lists. The response rate was 97.3% in this survey. Sociodemographic status, lifestyle, health attitudes and the use of recommended preventive PHC services were surveyed by questionnaire. The relationship between the use of preventive services and patient characteristics were analysed using hierarchical regression models in a subsample of 1659 survey participants with a known diagnosis of hypertension or diabetes mellitus.

Results: Rates of PHC service utilization varied from 18.0% to 97.9%, and less than half (median: 44.4%; IQR: 30.8–62.5) of necessary services were used by patients. Patient attitude was as strong of an influencing factor as demographic properties but was remarkably weaker than patient socioeconomic status.

Conclusion: These findings emphasize that PHC performance indicators have to be evaluated concerning patient characteristics.