Childhood asthma and mould in homes-A meta-analysis.

Asthma is a multifaceted and multicausal disease. Childhood asthma is strongly influenced by genetic traits and is characterized by hyperreactivity of the airways so that also unspecific triggers including moulds can trigger an asthma attack. Therefore, it is undisputed that moulds in the home can cause asthma attacks in asthmatic children. It is, however, unclear if mould in homes also induce the development of asthma. Because more and more severe attacks in asthmatic children living in mouldy homes might speed up the diagnosis of asthma, cross-sectional studies are not well-suited to differentiate between mould as a causative or only as a precipitating factor. Cross-sectional studies show an increased asthma risk and poorer lung function in children living in mouldy homes. To better understand the causal role of mould in homes, a systematic review was performed with random effects meta-analysis focusing on cohort and case-control studies only.We found 21 case-control and 11 cohort studies examining the association between mould at home and later advent of childhood asthma. According to the case-control studies, mouldy homes increase the risk of asthma by 53% (95 confidence interval [CI]: 42-65%) with no evidence of heterogeneity or publication bias. Risk estimates based on cohort studies were smaller with 15% (1-31%). The cohort studies also showed no publication bias but substantial heterogeneity (I2 = 60.5, p = 0.005). Heterogeneity could be partly explained by percentage of male children, age of participants, and publication year, but was not affected by study quality.In conclusion, living in mouldy homes during childhood seems to increase the risk of later developing bronchial asthma.

Cognitive control adjustments are dependent on the level of conflict.

The congruency sequence effect (CSE) is one of the most investigated effects in the cognitive control literature. The conflict monitoring theory suggests that the CSE is the result of adjustments in cognitive control based on perceived conflict. A recent paper by Zhang and colleagues, has investigated whether the manipulation of conflict level by changing distractor incompatibility in a flanker task affects the amount of adjustments in cognitive control. Their study produced mixed findings, somewhat supporting the original conflict monitoring theory, but also suggesting other explanations, such as the repetition expectancy account. We replicated the experimental design in a multisite online study (N = 347), with Hungarian, Italian, and Singaporean participants. Our results supported the prediction that changes in the level of conflict trigger conflict adaptation, revealing that increasing conflict levels induced stronger adaptive control. Bayesian hypothesis testing indicated a monotonic reduction in congruency effects as a function of previous conflict strength. This finding is in line with the extension of the traditional conflict monitoring theory, as well as other theories like affective signaling and expected value of control, implying that the relationship between conflict and interference effects is gradual, rather than a binary function.

The role of liver-specific contrast-enhanced MRI before resection of colorectal liver metastases / Májsejtspecifikus kontrasztanyaggal végzett MR-vizsgálat alkalmazása colorectalis eredetu májáttétek reszekciója elott.

Összefoglaló. Bevezetés: A colorectalis eredetu májáttétek (CRCLM-ek) kuratív célú kezelésében elsodleges a sebészi reszekció. A mutét elott különbözo képalkotó vizsgálatok végezhetok, az egyik ilyen speciális vizsgálat a májsejtspecifikus kontrasztanyaggal végzett MR-vizsgálat. Célkituzés: Tanulmányunkban a májsejtspecifikus kontrasztanyaggal végzett MR-vizsgálat helyét és szerepét vizsgáltuk a májsebészeti gyakorlatban colorectalis áttétes betegek esetében. Módszer: Az Uzsoki Utcai Kórház Sebészeti-Onkosebészeti Osztályán 2017. 01. 01. és 2019. 12. 31. között CRCLM miatt májreszekcióra kerülo betegek adatait elemeztük. Retrospektív módon vizsgáltuk a betegek általános sebészeti és onkosebészeti paramétereit, a képalkotó diagnosztikai eredményeket, a mutéti adatokat és a patológiai leleteket. Eredmények: 132, CRCLM miatt operált betegbol 73 szoliter áttét (55%), míg 59 beteg (45%) többszörös áttét miatt került mutétre. 94 betegnél (71%) történt májsejtspecifikus MR-vizsgálat. Szoliter áttét esetén 60%-ban, multiplex áttétek esetén 85%-ban történt májsejtspecifikus MR-vizsgálat (p = 0,02). A szoliter áttétes betegek 8%-ában, míg a multiplex áttétes betegek 39%-ában mutatott további áttétet a májspecifikus kontrasztanyaggal végzett MR-vizsgálat (p = 0,001). A betegek 5%-ában igazolódott fals pozitivitás és 6%-ában fals negativitás a májsejtspecifikus MR-vizsgálat során. 264 góc vizsgálata alapján a májspecifikus kontrasztanyaggal végzett MR-vizsgálat szenzitivitása CRCLM esetén 95%-os, míg pozitív prediktív értéke 93%-os volt vizsgálatunkban. Következtetés: A májsejtspecifikus kontrasztanyaggal végzett MR-vizsgálat hasznos diagnosztikai módszer a CRCLM-ek sebészi reszekciója elott. Leginkább többszörös áttétek esetén, preoperatív szisztémás onkológiai kezelést követoen, illetve más képalkotó vizsgálaton igazolt eltunt áttét esetén javasolható az alkalmazása. Orv Hetil. 2021; 162(50): 2010-2016. INTRODUCTION: Liver resection is the only curtive treatment option of colorectal cancer liver metastases (CRCLMs). While different diagnostic modalities are available before surgery, a specific diagnostic tool is the liver-specific contrast-enhanced MRI. OBJECTIVE: The purpose of this study was to evaluate the role of liver-specific contrast-enhanced MRI before resection of colorectal liver metastases. METHOD: Patients with CRCLM, resected at the Department of Surgical Oncology, Uzsoki Teaching Hospital, between 01. 01. 2017 and 31. 12. 2019 were enrolled in our study. Clinical data, diagnostic, intraoperative and pathological findings were analyzed in a retrospective setting. RESULTS: 132 CRCLM patients were resected in this period, 73 patients had solitary (55%), and 59 patients (45%) had multiple metastases. Liver-specific contrast-enhanced MRI was performed in 94 patients (71%). 60% of the patients with solitary and 85% of the patients with multiple CRCLM had liver-specific contrast-enhanced MRI (p = 0.02). Compared to other modalities, liver-specific contrast-enhanced MRI showed additional metastases in 8% of the patients with solitary, and in 39% of the patients with multiple metastases (p = 0.001). Liver-specific contrast-enhanced MRI had a 5% false-positivity and a 6% false-negativity rate. 264 leasions were analyzed, and the sensitivity of the liver-specific contrast-enhanced MRI was 95% with a predictive positive value of 93%. CONCLUSION: Liver-specific contrast-enhanced MRI is a useful diagnostic tool in CRCLM patients before liver resection. It is highly recommended in the case of multiple metastases, after preoperative chemotherapy and in the case of disappearing metastases. Orv Hetil. 2021; 162(50): 2010-2016.

Development and Initial Testing of a Modified UroVysion-Based Fluorescence In Situ Hybridization Score for Prediction of Progression in Bladder Cancer.

OBJECTIVES: Our aim was to predict progression of non-muscle-invasive bladder urothelial carcinomas (NMIUCs) into muscle-invasive disease by assessing cytogenetic abnormality of tumors with a new UroVysion scoring system. METHODS: Seventy-five bladder cancer cases (including 57 NMIUCs) were classified according to the quantitatively assessed degree of UroVysion-detected chromosomal abnormalities into urine fluorescence in situ hybridization score (UFS) groups: UFS I, II, and III. Cox time-to-event, Kaplan-Meier, and C-statistics analyses were performed. RESULTS: UFS proved to be an independent prognostic factor of progression-free survival (PFS) and time to progression (TTP). NMIUCs with UFS III had a 34.05-fold increased hazard for progression to muscle-invasive cancer (TTP; 95% confidence interval, 5.841-198.5; P < .001) in comparison with UFS I to II cases. The addition of UFS to conventional risk scores increased the C-index for PFS and TTP. CONCLUSIONS: UFS can indicate an increased risk for progression into muscle-invasive disease in patients with NMIUC and improves prognostic accuracy of the current clinical risk assessment systems.

Epidemiology and Treatment Guidelines of Negative Symptoms in Schizo-phrenia in Central and Eastern Europe: A Literature Review.

AIM: To gather and review data describing the epidemiology of schizophrenia and clinical guidelines for schizophrenia therapy in seven Central and Eastern European countries, with a focus on negative symptoms. Methods : A literature search was conducted which included publications from 1995 to 2012 that were indexed in key databases. Results : Reports of mean annual incidence of schizophrenia varied greatly, from 0.04 to 0.58 per 1,000 population. Lifetime prevalence varied from 0.4% to 1.4%. One study reported that at least one negative symptom was present in 57.6% of patients with schizophrenia and in 50-90% of individuals experiencing their first episode of schizophrenia. Primary negative symptoms were observed in 10-30% of patients. Mortality in patients with schizophrenia was greater than in the general population, with a standardized mortality ratio of 2.58-4.30. Reasons for higher risk of mortality in the schizophrenia population included increased suicide risk, effect of schizophrenia on lifestyle and environment, and presence of comorbidities. Clinical guidelines overall supported the use of second-generation antipsychotics in managing negative symptoms of schizophrenia, although improved therapeutic approaches are needed. Conclusion : Schizophrenia is one of the most common mental illnesses and poses a considerable burden on patients and healthcare resources alike. Negative symptoms are present in many patients and there is an unmet need to improve treatment offerings for negative symptoms beyond the use of second-generation antipsychotics and overall patient outcomes.

Effects of Geographical Accessibility on the Use of Outpatient Care Services: Quasi-Experimental Evidence from Panel Count Data.

In 2010-2012, new outpatient service locations were established in Hungarian micro-regions, which had lacked such capacities before. We exploit this quasi-experiment to estimate the effect of geographical accessibility on outpatient case numbers using both individual-level and semi-aggregate panel data. We find a 24-27 per cent increase of case numbers as a result of the establishments. Our specialty-by-specialty estimates imply that a 1-min reduction of travel time to the nearest outpatient unit increases case numbers for example by 0.9 per cent in internal care and 3.1 per cent in rheumatology. The size of the new outpatient capacities has a separate effect, raising the possibility of the presence of supplier-induced demand. By combining a fixed-effects logit and a fixed-effects truncated Poisson estimator, we decompose the effects into increases in the probability of ever visiting a doctor on the one hand and an increase of the frequency of visits on the other hand. We find that new visits were dominant in the vast majority of specialties, whereas both margins were important for example in rheumatology. Finally, we demonstrate the usefulness of the fixed-effects truncated Poisson estimator in modelling count data by examining its robustness by simulations.

A novel orally active inhibitor of HLE.

Human leukocyte elastase (HLE) is a serine proteinase, capable of degrading a variety of structural matrix proteins. SSR69071 2-[(4-isopropyl-6-methoxy-1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methoxy]-9-(2-piperidin-1-ylethoxy)-4H-pyrido[1,2-a]pyrimidin-4-one was selected as a novel orally active HLE inhibitor for treatment of chronic obstructive pulmonary diseases, asthma, emphysema, cystic fibrosis and several inflammatory diseases (WO 01/44245 A1) (J. Pharm. Exp. Ther., submitted for publication).

Biochemical and pharmacological characterization of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yloxymethyl)-4-(1-methylethyl)-6-methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (SSR69071), a novel, orally active elastase inhibitor.

Human leukocyte elastase (HLE) is a proteinase capable of degrading a variety of proteins. Under normal circumstances, the proteolytic activity of HLE is effectively controlled by its natural inhibitors. However, an imbalance between elastase and its endogenous inhibitors may result in several pathophysiological states such as chronic obstructive pulmonary disease, asthma, emphysema, cystic fibrosis, and chronic inflammatory diseases. It is anticipated that an orally active HLE inhibitor could be useful for the treatment of these diseases. 2-(9-(2-Piperidinoethoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yloxymethyl)-4-(1-methylethyl)-6-methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (SSR69071) is a potent inhibitor of HLE, with the inhibition constant (K(i)) and the constant for inactivation process (k(on)) being 0.0168 +/- 0.0014 nM and 0.183 +/- 0.013 10(6)/mol sr, respectively. The dissociation rate constant, k(off), was 3.11 + 0.37 10(-6)/s. SSR69071 displays a higher affinity for human elastase than for rat (K(i) = 3 nM), mouse (K(i) = 1.8 nM), and rabbit (K(i) = 58 nM) elastases. Bronchoalveolar lavage fluid from mice orally treated with SSR69071 inhibits HLE (ex vivo), and in this model, SSR69071 has a dose-dependent efficacy with an ED(50) = 10.5 mg/kg p.o. SSR69071 decreases significantly the acute lung hemorrhage induced by HLE (ED(50) = 2.8 mg/kg p.o.) in mice. Furthermore, SSR69071 prevents carrageenan- (ED(30) = 2.2 mg/kg) and HLE-induced (ED(30) = 2.7 mg/kg) paw edema in rats after p.o. administration. In conclusion, SSR69071 is a selective, orally active, and potent inhibitor of HLE with good penetration in respiratory tissues.