No subscale of HL made a significant contribution to the amount of daily PA . Not all subscales of HL seem to have an influence on the occurrence of healthy behavior, such as PA. This should be considered when HL-based interventions are designed. Further investigation of the relationship between HL and PA is needed. Objective assessments of both HL and PA can provide additional information for this task.Studies show that high health literacy (HL) can support the promotion and maintenance of healthy behavior such as physical activity (PA). However, most studies rely on subjective data. The aim of the present study is to investigate the relationship between HL and PA, not only with subjectively but also with objectively measured PA data. The present study is a pooled analysis of baseline data from the research association TRISEARCH (2015–2018), which focused on the HL of working adults. HL was measured by Lenartz’ questionnaire, and PA by the Global Physical Activity Questionnaire . A subsample (n = 124) also received accelerometers (Actigraph GT3X+) to provide more objective PA data. Partial correlations and regression models were used to investigate the relationship between HL and questionnaire- and accelerometer-derived PA. Very low and medium partial correlations could be found for HL subscales and daily PA by questionnaire (r = −0.06,  Health-related competencies or health literacy (HL) are defined as “cognitive and social skills which determine the motivation and ability of individuals to gain access to, understand and use information in ways which promote and maintain good health” . Studieshealth behavior and health are the result of two basic and six secondary abilities, all of which define HL. In this model, basic knowledge of health and basic skills concerning health build the foundation, e.g., the ability to read health-related manuals [self-perception includes the perception of one’s own needs and feelings as well as the focus on internal and external processes , which again are part of self-regulation [proactive approach to health), self-perception influences even more secondary abilities: Dealing with health information describes the capability to understand health-related information and integrate it into one’s personal life. Someone with high self-control is disciplined in pursuing personal goals [self-regulation, e.g., being able to relax) [communication and cooperation describes behavior which intends to establish and maintain good relationships with others [The validated structural model of HL introduced by Lenartz  and Soel manuals  and unde manuals . These bgulation ,10. Togeal goals , whereaso relax) . Lastly,h others . One of the most common methods in maintaining health and decreasing the risk of non-communicable diseases is physical activity (PA) ,15,16,17The present study is a pooled analysis of baseline data from studies by the research association TRISEARCH, which had the overarching objective to assess and improve HL in different target groups in the workplace . For theData collection took place between 2015 and 2018 within the baseline assessments of the three studies. All participants provided written informed consent.self-regulation , self-control , self-perception , proactive approach to health , communication and cooperation , and dealing with health information  [HL was derived from the German questionnaire by Lenartz . The que to me”) . The sco to me”) ,25.The subjectively perceived amount of PA was measured by the Global Physical Activity Questionnaire (GPAQ) . The GPAA subsample of each subproject additionally received accelerometers (Actigraph GT3X+) to provide objective data on PA. Wearing the accelerometer was voluntary, as a previous study  showed nOn the basis of GPAQ and Actigraph data, daily and weekly minutes of MVPA as well as daily MET  of MVPA were calculated. The MET refers to the energy cost of an activity , where aSince no instruction for handling missing values was provided by Lenartz , the autDescriptive statistics  were calculated for demographic characteristics, HL and PA based on the questionnaires and accelerometers. For the investigation of the overall relationship between PA and HL, partial correlations were used for the objective and subjective measurement of PA and the subscales of the Lenartz questionnaire. Since previous studies have shown that physical activity and health literacy differ by sex and age ,39,40, sself-regulation, self-control, self-perception, proactive approach to health, communication and cooperation and dealing with health information), sex  and age as independent variables. The analyses were performed for both objective and subjective measures. Regression models were used to investigate the influence of HL on the amount of PA. For this purpose, two linear regression models were used for subjectively and objectively assessed MVPA as dependent variables, respectively, and the subscales of HL  of them male, mean age 32.5 (14.5) years, were recruited. After applying the eligibility criteria for the present analyses, 1037 participants were included in the pooled sample. Of those, a total of 156 participants (15.0%) received an accelerometer and 107 provided sufficient data. self-regulation, proactive approach to health and communication and cooperation, a mean value of 2.6 (0.6) was calculated. The mean value for the subscale self-control was 2.9 (0.5), for self-perception was 3.0 (0.5), and for dealing with health information was 3.0 (0.6).Descriptive statistics for the subjective and objective PA measurements are described in self-perception showed a very low negative partial correlation with daily MET of MVPA  and daily vigorous PA .For the subjective measurement, the subscale proactive approach to health and daily vigorous PA  was found. All other partial correlation analyses were non-significant (p > 0.05). When looking at the data drawn from the accelerometers, one statistically significant medium positive partial correlation between the subscale p > 0.05, GPAQ: adjusted R² < 0.01, Actigraph GT3X+: adjusted R² = 0.06, see p < 0.05).For both regression analyses, no aspect of HL made a significant contribution to the amount of daily MVPA . In regard to the objective PA levels, one medium correlation with the subscale proactive approach to health was found. Since the majority of HL subscales showed no connection to PA at all, these results indicate that not all aspects of HL might be equally important for promoting and maintaining healthy behavior.The aim of the present study was to investigate whether a relationship between HL and PA measured by subjective and objective instruments exists. In total, the study population reported moderate to high values for HL and PA. The hypothesized positive correlation between HL and PA was only partly confirmed. Only one very low correlation could be observed for the subjective assessment of PA and one subscale of HL  but not with work time MET minutes. This supports the assumption that if the importance of health-promoting behavior is internalized and a person takes active responsibility for showing such behavior, increased vigorous PA might be the result and be shown in leisure time.The present study only partly confirms previous research which showed a connection between HL and PA ,20,42. N Lenartz , the pro jogging . Such ac jogging  have sho jogging ,46. In lself-perception, neither the regression analyses nor the data from the accelerometry showed any connection at all. A possible explanation for these results may refer to the perception of PA. As previous studies have shown, self-reported PA in terms of intensity and duration differs from data recorded by more objective tools [self-perception on the data measured by accelerometry was found. In addition to those findings, a result that is controversial in relation to the literature was found: Lenartz’ assumptions and previous results, which postulated that a greater ability in perceiving inner and outer processes results in a healthier lifestyle and adaptive health behavior , could nve tools ,49. PA ove tools . Therefove tools ,52 as weAlthough the strongest correlation between HL and PA was found within the Actigraph GT3X+ data, it is questionable whether the objective measurement and the resulting more valid estimation of PA  has a coThe present study was conducted as a pooled analysis of three projects by the research association TRISEARCH, which were addressing different target groups. Due to the cross-sectional study design, testing the direction of causality between HL and PA was not possible. Moreover, large differences between the different target groups regarding age and sex were present. One project was conducted with apprentices, who were at the start of their working career and, therefore, much younger. Research showed that younger age was a significant predictor for lower HL levels . AdditioIn the present study, HL was assessed with a questionnaire generated by the German researcher Lenartz. This questionnaire is not yet as commonly used as the Health Literacy Questionnaire (HLQ) . The HLQA problem that might occur when both PA and HL are measured via questionnaires is that both measurements underlie the probability of recall and social desirability bias. Recall or social desirability bias could, for instance, influence the participants’ response when recalling the length and occurrence of PA behavior . People Due to these limitations, the generalizability of the Actigraph GT3X+ results must be treated with caution. Hence, further studies with objective measures of HL and healthy behavior are needed to improve the understanding of the underlying mechanisms of this relationship.The present study suggests that not all subscales of HL influence the occurrence of healthy behavior—such as PA—in the same way. More research on the different components of HL and their particular influence on specific health behaviors is needed to improve the quality of HL-based interventions for promoting healthy behavior. As the results indicate, making sure that people take responsibility for their own health seems like a promising approach.


Background: Cerebral venous sinus thrombosis (CVST) in children is rare in a clinical setting. The aim of this study was to summarize the etiological, clinical, and imaging characteristics of CVST in children.Methods: We retrospectively analyzed the data of 30 patients with a diagnosis of CVST who were admitted to Children's Hospital of Fudan University from 2008 to 2018. The medical records, including clinical manifestations, laboratory data, neurological findings, treatment, and short-term prognosis were analyzed.Results: Etiologically, the causes of CVST were infection (7/30), tumor (3/30), nephritis or nephrotic syndrome (8/30), traumatic brain injury (1/30), and undefined disease (11/30). All 30 cases were diagnosed with CVST after a neuroimaging examination using brain magnetic resonance imaging (MRI) combined with magnetic angiography venography (MRV). With regard to short-term prognosis, all the patients were treated with anticoagulants, after which 26 cases improved.Conclusions: CVST patients do not typically present with specific clinical manifestations, which leads to a high rate of misdiagnosis and delayed therapy. Increased consideration and prompt MRV checkup plays a key role in achieving an accurate diagnosis. Overall, anticoagulation is a safe and effective treatment for CVST. Cerebral venous sinus thrombosis (CVST) is a particular type of cerebrovascular disease accompanied by focal cerebral edema. Intracranial hypertension, venous cerebral infarction, and seizures are the most prominent clinical features of CVST , 2. NeonMedical records of patients admitted to our hospital between 2008 and 2018 were retrospectively reviewed to identify potential subjects. All patients <18 years old with CVST confirmed by MRV were included in this study. No exclusion criteria were used. We collected the following types of data from the medical records: (i) general conditions, including gender, age, and past history; (ii) disease state including the time from onset to diagnosis, etiology, clinical symptoms, and signs; (iii) imaging features; (iv) laboratory tests, including platelets, white blood cells, C-reactive protein, and coagulation function; (v) short-term prognosis (state at discharge).The study was approved by the ethics committee at Children's Hospital of Fudan University. Due to the retrospective design of this study, informed consent was waived.Continuous data were expressed as median and interquartile range and categorical data were expressed as absolute numbers and percentages. Statistical Package for the Social Sciences software (version 25.0) was used for data analysis.Thirty subjects were identified based on the selection criteria. The information system in our hospital was updated in 2012 and some data were missing. Therefore, the imaging and laboratory data were only obtained for 20 patients. Some patients initially received CT and MRI and were further confirmed by MRV. We found that (1) for the head CT examination, the density of the anterior sagittal sinus was raised in 2 cases . Twenty six patients had improved clinical symptoms, 2 patients died, and 2 were transferred to another hospital. Of the two patients that died, one deteriorated rapidly and eventually died due to intravenous sinusitis; the other had underlying diseases , which progressed rapidly after onset leading to death. Warfarin was used for 3 months after discharge; the initial dose was 0.1–0.2 mg/kg/d. Blood coagulation function was monitored every 2–4 weeks and warfarin dose was set to maintain the INR at 2.0–3.0. After a 3-month follow-up, 21 patients were found to have improved. No bleeding complications were observed. The clinical symptoms did not recur and visual acuity improved.The clinical manifestations of CVST are complex and variable; they lack specificity, sometimes making it difficult to diagnose early. The literature reports that the early diagnosis and treatment of CVST could reduce the mortality rate to 5–15% . TherefoPediatric CVST occurs due to both intravascular and vascular factors, and dehydration is a common risk factor for all ages. The literature reports that one-third to two-thirds of children with CVST are in a pre-thrombus state . In thisBecause of the different etiologies and locations of the affected sinus, the clinical manifestations of CVST are diverse and lack specificity. Thus, it is extremely difficult to diagnose CVST based on clinical manifestations alone. The disease could present with an onset that is acute, subacute, or chronic. An uncharacteristic headache is a common clinical symptom, and 90% of patients have complaints of a headache as reported from international papers . There wNeuroimaging is the principal basis for the diagnosis of CVST . TypicalAt present, the treatment for CVST is based primarily on adult cases. The purpose of CVST anticoagulant therapy is to avoid thrombus enlargement and contribute to spontaneous thrombolysis . StudiesBecause of the retrospective analysis of clinical data, there are some limitations in this study. The first limitation is that the definite underlying causes were not identified in 11 patients. Second, the follow-up time was only 3 months and a longer follow-up is needed in future studies. Third, genetic tests were not conducted in our institution; therefore, we were unable to obtain these data.It is important to achieve an early diagnosis with CVST. Therefore, we believe that CVST should be highly suspected in the following clinical situations: (1) patients who have high risk factors for venous sinus thrombosis; (2) those with progressive intracranial hypertension, no obvious signs of neurolocalization, particularly those with normal CT scans; (3) sudden onset of focal system damage, such as due to cerebral infarction, but the lesion does not conform to the distribution of arteries, or the effect is not obvious after treatment according to the cerebral infarction; (4) there is no obvious cause of decreased vision, disturbance of consciousness accompanied by or without seizures, and the disease progresses rapidly; and (5) headache, vomiting, meningeal irritation, and cerebrospinal fluid changes that cannot be explained by other known causes such as encephalitis, meningitis, or bleeding.In summary, CVST is prevalent in the pediatric population and etiology of this disease is complex. Because of the lack of specific clinical manifestations, the rate of misdiagnosis is high. Clinicians should carefully look for evidence of the disease, perform neuroimaging in a timely manner for early diagnosis, and give appropriate treatment as early as possible to improve prognosis and decrease complications.All datasets generated for this study are included in the manuscript/supplementary files.X-HW contributed to the analysis, interpretation of the data, and drafting of the manuscript. L-MZ, Y-MC, JW, and L-FY performed the analysis and interpretation of the clinical data. S-ZZ conceived, designed, supervised the study, interpreted the data, and drafted and revised the manuscript content. All the authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Aplysina archeri (Aplysineidae: Verongiida) is well known to contain bromotyrosines with relevant bioactivity against human and animal diseases. The aim of this study was to develop an express method for the production of naturally prefabricated 3D chitin and bromotyrosine-containing extracts simultaneously. This new method is based on microwave irradiation (MWI) together with stepwise treatment using 1% sodium hydroxide, 20% acetic acid, and 30% hydrogen peroxide. This approach, which takes up to 1 h, made it possible to isolate chitin from the tube-like skeleton of A. archeri and to demonstrate the presence of this biopolymer in this sponge for the first time. Additionally, this procedure does not deacetylate chitin to chitosan and enables the recovery of ready-to-use 3D chitin scaffolds without destruction of the unique tube-like fibrous interconnected structure of the isolated biomaterial. Furthermore, these mechanically stressed fibers still have the capacity for saturation with water, methylene blue dye, crude oil, and blood, which is necessary for the application of such renewable 3D chitinous centimeter-sized scaffolds in diverse technological and biomedical fields.Sponges are a valuable source of natural compounds and biomaterials for many biotechnological applications. Marine sponges belonging to the order Verongiida are known to contain both chitin and biologically active bromotyrosines.  Chitin is composed of β1,4)-linked N-acetyl-glucosamine units and represents the most abundant structural polysaccharide of invertebrates, including such marine phyla as sponges, corals, annelid worms, mollusks, and arthropods ,4-linked. Chitin Industrial deproteinization is carried out using a base solution of KOH or NaOH . TheDemineralization can be achieved using chelators (ethylenediamine tetraacetic acid-EDTA ), or varA schematic overview of biological and chemical methods of chitin isolation for obtaining chitosan, following the example of crustacean sources based on the literature reports cited above, is presented in Unlike chitin of crustacean origin, poriferan chitin has never been used as a source for chitosan. Besides spongin , chitin Since 2007, when chitin in the form of 3D scaffolds was isolated from selected demosponges for the first time , chitin 3COOH) extraction steps, enabling the desilicification and decalcification of the mineralized sponge skeleton, has been used    and acidic . Pigellidae)  44]. An. An3COOHellidae) , enablinA. archeri became completely soft, colorless, and demineralized in a time of 114 h. However, the application of microwaves (750 W and 2450 MHz), as reported here, decreased the treatment time to only 55 min. The most time (33 min) was taken by the water rinsing procedures. The estimated chitin content in the skeletons of A. archeri is ~5% by weight.The investigated sponge belongs to the family Aplysinellidae (order Verongiida), and hence is reported as a renewable source of chitin  as wA. archeri, with the microwave approach also displaying the typical fibrous structure with concentric layers typical for microtubular chitin, previously reported in other representatives of the family Aplysinellidae + (m/z 162.08), the specie of sodium ion bound dGlcN monomer [M + Na]+ (m/z 202.07), and the noncovalent dimer [2M + Na]+ (m/z 381.15). A similar proton-bound GlcN covalent dimer with m/z = 359.17 was observed in the spectra. Together, these data indicate the high purity of the chitin in the A. archeri scaffold.Additionally, we used electrospray ionisation mass spectrometry (ESI-MS) for identification of rganisms ,47 and frganisms . The ESIstandard b. These A. archeri into chitosan under the conditions applied. Consequently, we decided to use both ATR-FTIR and Raman spectroscopy as highly sensitive methods to investigate this possibility. To exclude the possibility of deacetylation during the isolation of chitin with the microwave approach , and its intensity is significantly lower. As an additional feature, the characteristic intense bands at 945 cm−1 and 950 cm−1, attributed to wagging vibrations of CHx, are observed only in the isolated scaffold and the α-chitin standard, respectively  3D chitin scaffold isolated from rude oil . The samRinsing the scaffold contaminated with crude oil d in a soA. archeri chitin microfibers, is very visible . It has been recognized that chitin of crustacean origin induces blood coagulation by adhering to platelets, forming a chitin/platelet complex that accelerates the polymerization of the fibrin monomer to form a blood clot . ConseqA. archeri, obtained by the microwave-assisted method, can be used as a potential sorbent for MB. The swelling capacity of these scaffolds, with respect to water, was measured at 255 ± 8%. It should be noted that adsorption of the dye occurs on the surface as well as within the chitinous microtubes, and the dye could not be removed from the chitin by simply washing the chitin in hot distilled water , Young modulus, etc. Obviously, we will present these data in comparison with chitin of crustacean and fungal origins.One of the most promising applications of ready-to-use chitinous microtubular scaffolds of sponge origin is biomedicine. However, it should be noted that both natural as well synthetic biopolymer-based three-dimensional, open pore scaffolds have evolved as gold standards for biomedicine in recent applications, owing to their superior role in tissue regeneration . Three-dIanthella basta, that growth and regeneration rates in this sponge were sufficient to secure a supply for potential biomedical application. Further studies with other Verongiid sponges will be needed to establish this order of sponges as a viable source of chitin scaffolds and to enable the use of these naturally prefabricated constructs in biomedical applications.However, if the large-scale testing and application of chitin scaffolds is to be promoted, it will be necessary to secure the supply of such sponges via aquaculture , as wildAplysina archeri (Higgin 1875), were collected at depths of 10–25 m by scuba divers around the Caribbean islands of Saint Vincent and Curaçao in May 2015 and June 2017, during the Pacotilles expedition. All permits that were required for the described study were obtained during this expedition and complied with all relevant regulations. The species was identified by A. Ereskovsky.Samples of the demosponge, A. archeri was performed by a modification of the well-known standard method [The isolation of the chitin scaffold from d method . FirstlyA. archeri was cut into pieces 5 cm × 2 cm in size and used for chitin isolation. The isolation procedure is presented schematically in 2O2 treatment at pH~10 under MWI for 1 min and then washed with distilled water until a neutral pH was reached.The sample material of Hydrogen peroxide was chosen for bleaching because it is reported that hydrogen peroxide in a microwave field, under the conditions of the experiment, does not cause significant changes in the chemical structure of the polymer ). Steps The isolated chitin fibers were observed using a BZ-9000 instrument  in fluorescent and light microscopy mode.A. archeri skeletons were investigated with light and fluorescent microscopy before and after staining with CFW . For staining, 20 µL of a solution of 10 g glycerin and 10 g NaOH in 90 mL water was applied. After 15 s, the CFW was added and kept for 30 min in darkness at room temperature. The fibers were washed with distilled water to remove unattached CFW and then dried at room temperature.Upon binding with polysaccharides, calcofluor white (CFW) enhanced their fluorescence. The isolated fibers from the selected Streptomyces griseus  was added. In the following 10 h, the microscope documented the digestion of the fibers by taking light field and fluorescent images every 30 min.To observe the chitinase digestion process of the fibers isolated from sponge skeletons, the BZ-9000 instrument was used in light and fluorescent microscopy mode. Single fibers were rinsed with 50 mL phosphate buffer (pH 6.0). After the removal of the phosphate buffer, chitinase from a-chitin standard  and a chitosan standard (Sigma-Aldrich) were recorded. Postprocessing of the recorded spectra was performed with OriginLab 2015.Infrared spectroscopy was used for qualitative analysis of the isolated fibers. ATR-FTIR  spectra were recorded with the Nicolet 380 FTIR spectrometer . The spectra were analyzed with appropriate software . In addition to the spectra of the fiber material, spectra of the TM, Kaiser Optical Systems Inc., Ann Arbor, MI, USA) coupled with a light microscope . The laser beam had a power of 400 mW, which resulted in 110 mW at the sample due to the transmission of the microscope optics. The spectral range was from 200 to 3250 cm−1, with a set resolution of 4 cm−1. For improvement of the signal-to-noise ratio, the integration time was set to 1 s and an addition of 50 spectra was performed. The baseline was implemented with MATLAB  and further postprocessing was carried out with OriginPro 2015.Raman spectra were recorded with a Raman spectrometer . Samples were fixed on a sample holder with carbon patches, and these were then covered with carbon or with a 5–10 µm gold layer using an Edwards Sputter Coater S150B .The elements were analyzed by energy dispersive X-ray spectroscopy in the EDX analysis system from EDAX  and XL 30 ESEM Philips-Scanning Electron Microscope .Samples were prepared for ESI-MS as follows. The isolated chitin scaffold was hydrolyzed in 6M HCl for 24 h at 90 °C. The resulting solution was filtered with a 0.4-micron filter, and the filtrate was freeze-dried to remove excess HCl. The solid residue was dissolved in water for ESI-MS analysis. Standard d-glucosamine, used as a control, was purchased from Sigma . All ESI-MS measurements were performed on an Agilent Technologies 6230 TOF LC/MS spectrometer . Nitrogen was used as a nebulizing and desolvation gas. Graphs were generated using Origin 8.5 for PC.For the sorption experiments, crude oil , pig blood  and methylene blue (Sigma-Aldrich) were used.Sm is the mass of the swollen sponge chitin and dm is the mass of the dry sponge chitin.The swelling capacity (water) of isolated 3D chitinous scaffolds was calculated using the following formula :SwellingA. archeri has been proven for the first time. Furthermore, microwave-assisted demineralization and deproteinization have been established as new and rapid methods for both chitin and pigment extraction from verongiid demosponges. It has been demonstrated, beyond a doubt, that the new approaches enable a significant improvement in the time efficiency of chitin isolation from Verongiida sponges without destruction of the unique fibrous interconnected structure of the isolated biological material. Furthermore, these mechanically stressed fibers still have the capacity for saturation with water, methylene blue dye, crude oil, and blood, which will be crucial for future applications of such naturally prefabricated 3D chitinous centimeter-sized scaffolds in diverse technological and biomedical fields. As the analysis of the isolated scaffolds has shown, under the conditions studied here, the microwaves do not deacetylate the chitin to chitosan. The method proposed in this study both reduced the consumption of the aggressive chemicals as well as drastically reduced the time of chitin extraction. Therefore, microwave assisted extraction is a viable, cost efficient, and fast method for the production of chitin scaffolds from marine sources.In this study, the presence of chitin in the skeleton of


Lots of previous reports have suggested a potential association of atopic dermatitis (AD) with stroke and myocardial infarction (MI). However, the result is still controversial, Consequently, we conducted this meta-analysis to estimate the relationship of AD with Stroke and MI.PubMed, Embase, and Web of Science databases were searched from inception to June 2018. Stroke and MI were considered as a composite endpoint. We calculated pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup and sensitivity analysis were performed to assess the potential sources of heterogeneity of the pooled estimation.P = .000) and MI , compared with participants without AD. The risk of stroke and MI was significant both in male subjects , but not in female subjects . The results were more pronounced for ischemic stroke  in the stratified with stroke type. Stratifying by AD type, the risk of stroke was significant in severe AD  and moderate AD  for MI.A total of 12 articles with 15 studies involving 3,701,199 participants were included in this meta-analysis. Of these, 14 studies on stroke and 12 on MI. Pooled analysis showed participants with AD experienced a significant increased risk of stroke (combined HR, 1.15; 95% CI, 1.08–1.22; AD is independently associated with an increased risk of stroke and MI, especially in male subjects and ischemic stroke and the risk is associated with the severity of AD. It has become the leading non-fatal burden to health attributable to skin diseases, and may increase the risk of the immune-mediated inflammatory diseases such as asthma and allergic rhinitis. This creates a major public health issue.Atopic dermatitis (AD) or atopic eczema is a chronic relapsing inflammatory skin disease which is characterized by drastic pruritus and eczema affecting both children and adults. Stroke and ischemic heart disease reminds a leading cause of death and a major cause of adult disability worldwide. Traditional factors such as hypertension, diabetes, hypercholesterolemia, cigarette smoking, and low level of physical activity increase the risk of stroke and myocardial infarction (MI).,7 Nowadays, it is generally accepted that atherosclerosis is a chronic systemic inflammation disease, which is the important reason of several serious adverse events, including coronary artery disease, MI, stroke, and peripheral artery disease. And research shows that many skin disorders are closely associated with stroke and MI.–12 It leads to a hypothesis that patients with AD may have an increase risk of stroke and MI, similar to inflammatory skin disorders.As everyone knows, cardiovascular disease (CVD) has become a major public health issue and is responsible for approximately 30% of all deaths worldwide.–24 However, the results are inconsistent. Some of these researches suggested that AD may increase the risk of stroke and/or MI incidence.,19,21,24 While several studies found that AD was not independently associated with increased risk of stroke and MI.,16,18 Furthermore, the different results of various studies showed that stroke type, sex, and severity of AD may affect the risk of stroke and/or MI independently.,19,21,22 Given these inconsistent results, to obtain a more comprehensive estimate of the putative influence of AD on stroke and MI, we conducted a meta-analysis to assess the association of AD with stroke and MI risk.During the past decade, research has suggested that AD is an allergic disease in which systemic inflammation involves more than just the skin, lots of epidemiologic observational studies have investigated the associations between AD and future stroke and/or MI.22.1As all analyses in our article were based on previously published studies, no ethical approval or patient consent was required.2.2 A systematic search of PubMed, EMBASE, and Web of Science databases was performed up to June 2018. The following key words were used in our search: “atopic dermatitis,” “atopic eczema,” “dermatitis” or “eczema” and “stroke,” “cerebrovascular diseases” or “cerebrovascular disorders,” and “myocardial infarction,” “coronary heart disease,” “ischemic heart disease.” Studies without language and race restrictions were included to avoid publication bias. Only human studies were included. Additionally, more articles were detected through a manual search of the references from retrieved publications and recent reviews. When there were several included studies from the same or similar participants data source, only the most recent study was chosen.The search was conducted according to the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement.2.3The following criteria were used in order to include the eligible studies: the study of adult patients had a cohort studies, case-control or cross-sectional design; AD was the exposure, stroke and/or MI was the outcome measure. Participants were free of stroke or MI at study entry; studies must report quantitative estimates of multivariate-adjusted odd ratio (OR) or relative risk (RR) or hazard ratio (HR) with 95% confidence interval (CI) for stroke and/or MI incidence or provided data for their calculation.2.4 The quality of the cohort study and case-control study was evaluated by the following 3 major components: the selection of the participants, the comparability between the groups and the ascertainment of the exposure. The modified NOS conducted by Herzog et al was used for cross-sectional study. Scores of 1 to 3, 4 to 6, and 7 to 9 were considered to be poor-, fair-, and good-quality studies, respectively.Two authors  independently extracted all data using a standardized data collection form. The discrepancies in data extraction were dealt with by consensus. We extracted the following data from each study: the first author's last name, year of publication, design of study, location of the participants, data source, number of participants, follow-up, exposure assessment, outcome assessment, and adjusted covariates. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies.2.5The odd ratios (OR) and relative risk (RR) were considered equivalent to HRs. Stata 12  was used to estimate the pooled HR and 95% CI of the association between AD with stroke and MI on the basis of a random-effects model meta-analysis. When a study reported the risk estimates adjusted for different covariates, we used the most full adjusted models in the analysis of the pooled HR. We converted HR and 95% CI into Napierian logarithms, and then we calculated the standard error (SE) from these logarithmic numbers and corresponding 95% CI.Q test statistic was used to examine the null hypothesis that the retrieved publications were evaluating the same effect at P < .10 level of significance, and I2 test statistic was used to quantify heterogeneity, which grades the inconsistency in these studies’ results. I2 values of 25, 50, and 75% was regarded as low, moderate, and high, respectively. Potential publication bias was assessed by the symmetry of the funnel plot, as well as the Egger test, and Begg test.,30Two methods were used to measure heterogeneity of HR across studies in this meta-analysis. The chi-square test based on Cochran P values were 2-sided and P < .05 was regarded as statistically significant.If there was evidence of heterogeneity, subgroup analyses and sensitivity analyses were employed to explain what contributed to the heterogeneity. Subgroup analyses based on adjusted HRs were conducted according to study type , sex , geographic area (Asia vs non-Asia), AD type , and stroke type (ischemic stroke vs hemorrhagic stroke). A sensitivity analysis was performed by removing each individual study from the meta-analysis to assess the possible reason for heterogeneity. In all statistic analysis, 33.1–24 The results of the study selection process are shown in Fig. A total of 629 articles were retrieved from the initial PubMed, Embase, Web of Science electronic database search. Of which 608 articles were excluded after the first screening based on titles and abstracts, leaving 21 articles for full-text review. Of these, 9 articles were excluded because data were not available in 2 publications, the articles were review in 4 publications, and the patients without AD in 2 publications, the outcome of interest was not stroke or MI in 1 publications. Finally, 12 articles were included in our meta-analysis. no specific follow-up time was indicated. Among these, 1 article had 2 studies, and 1 article had 3 studies. One study was conducted in the UK, 4 in Asia country (Taiwan),–21,24 3 in Demark,,18,23 4 in United States,,17 2 in Germany, and 1 in Canada. Among these, 5 were cross-sectional studies,,14,17 10 were cohort studies.–16,18–24 Three focused on stroke,,21,24 1 focused on MI and 11 on both.,20,22,23 All studies provided adjusted risk estimates, overall quality scores ranged from 7 to 9, and all studies were graded as good quality according to the Newcastle–Ottawa Quality Assessment Scale.The characteristics of the 12 retrieved articles with 15 studies were presented in Table 3.2P = .000). There was evidence of moderate heterogeneity in the magnitude of the association across studies . There was no evidence of publication bias by inspection of the funnel plot .The multivariable adjusted HRs of stroke in relation to AD from individual studies and the combined HR are presented in Fig. 3.3P = .014). There was evidence of modest heterogeneity in the magnitude of the association across studies . Review of funnel plots could not eliminate the potential for publication bias for MI .The multivariable adjusted HRs of MI in relation to AD from individual studies and the combined HR are presented in Fig.  MI Fig. B. While,3.4The subgroup analysis is shown in Table 3.5Sensitivity analysis was used to evaluate potential sources of heterogeneity in the association between the studies. To clear which one of the retrieved studies might influence the results, we assessed the risk estimates for the remainder of the studies by deleting 1 study at each turn. The results of the meta-analysis remained largely unchanged, indicating that the results of the present meta-analysis were stable .4In this meta-analysis of 15 studies involving 3,701,199 participants, we confirmed that AD was associated with an increased risk of stroke and MI. And the risk was significant in male subjects, but not in female subjects. In addition, results indicated that this risk was more common in ischemic stroke and was associated with the severity of AD. The pathogenesis of AD is attributed mostly to immune system abnormalities and hyperactivity, and mutation of several genes has been involved in the immune response, with key roles played by T-helper 2 (Th2) cell dysregulation and immunoglobulin E (IgE) production. In recent decades, overwhelming evidence has indicated that AD is associated with well-known risk factors for cardiovascular disease include hypertension, old age, diabetes mellitus, hyperlipidemia, and so on, while many of these are also associated with the risk of stroke and MI.–36 There is also some information that AD may have a direct role in the development of stroke and MI.,17,19,22 In addition, some believe that systemic inflammation associated with AD may increase the risk of cardiovascular and cerebrovascular diseases, similar to the increased risk of psoriasis, another chronic inflammatory skin condition.,38 However, the potential mechanisms by which AD is independently associated with an increased of stroke and MI remains ambiguous. We speculate that patients suffering from AD may have an increased risk of cardiovascular risk similar to psoriasis which has been confirmed as an independent cardiovascular risk factor. However, the inflammatory pathways of AD is differ with psoriasis, that AD is mostly mediated by Th2, and psoriasis by Th1 and Th17 cytokines. There are several possible explanations for the high risk of stroke and MI. First, AD was associated with increased blood platelet activation, which suggested that activated platelets play a role in the pathomechanism of AD. Chronic inflammatory changes of the vascular wall induced by platelet result in development of atherothrombosis. Second, reduced fibrinolysis was detected in patients with AD, which are known to be associated with prothrombotic tendency. Third, oxidative stress is likely to be an important factor in the pathogenesis of AD. Fourth, previous studies showed that AD has been associated with several cardiovascular risk factors, including obesity, decreased physical activity, increased smoking and alcohol assumption, hypertension, hyperlipidemia, and diabetes.,45 These mechanisms suggests that AD may be associated with a systemic effect which can lead to stroke and MI.AD is the most common chronic relapsing and inflammatory skin disease and its pathophysiologically characterized by abnormalities of epidermal barrier function and T-cell-driven cutaneous inflammation.,19,21,24 while 3 studies failed to find such an association.,16,18 A systematic review of AD and the risk of cardiovascular disease and type 2 diabetes in adults showed no association between AD and hypertension, presumed type 2 diabetes, myocardial infarction, and stroke in the quantitative crude data analyses and fully adjusted data analyses. But most studies were cross-sectional in this systematic review and information about sex, AD severity, and study type were lacking. In the present meta-analysis, we found that the risk of stroke and MI was higher in patients with AD and the male subjects. And similar analyses using fully cohort studies gave essentially identical results. This result is consistent with previous population-based cohort studies.,19–21 As we all known, men have been more frequently subjected to the negative influence factors, such as smoking, drinking, and other unhealthy behaviors, which may explain why male AD patients appear to have a higher risk of stroke and/or MI than female patients. Furthermore, results indicated that this risk was more common in ischemic stroke and was associated with the severity of AD, which was consistent with the conclusions of some large sample studies.–21,24 To our knowledge, stroke is divided into hemorrhagic stroke and ischemic stroke, although there are many vascular risk factors among the 2 major branches, but its pathophysiological basis is different, reflecting different pathogenesis. There is growing evidence to suggest that systemic inflammation can promote the progression of atherosclerosis and thrombosis to ischemic stroke,,48 therefor, changes in atherosclerosis and activation of the coagulation system related to chronic inflammation may be one of the reasons for high risk of ischemic stroke in AD patients.Over the past few decades, although the role of AD in cardiovascular or cerebrovascular diseases has been studied in previous clinical studies, it is not clear whether there is a causal link between AD with the risk of stroke and MI. Some studies suggested that AD is associated with an increased risk of stroke and/or MI incidence,Moderate heterogeneity across studies was observed, which did not alter much in the subgroup analyses and sensitivity analysis. Heterogeneity might have come from several sources, such as variations in characteristics of study populations, study designs, follow-up length, and adjustment for confounding factors. In the present meta-analysis, the sample size of each study, incomplete matching, country of origin, study type, and sex differences should be the main source of heterogeneity.Several potential limitations of the current meta-analysis should be acknowledged. First, there were different clinical designs in the included studies. Most of them were cohort studies, and 3 of them were cross-sectional studies. In these included studies, history of AD was mostly self-reported and not performed clinical evaluation or affirmed through any diagnostic testing, which may lead to recall bias. Second, confounding factors for the risk of stroke or MI were not adjusted consistently in these included studies. Medications use and history of asthma or other allergic diseases may affect the association between AD with stroke and/or MI risk. Other confounders like socioeconomic status, race, and lifestyle may also influence risk of stroke and/or MI. Third, the number of studies included in the subgroup was too small. Furthermore, the assessment standards of AD and stroke or MI in the included studies were different. Finally, language bias may be another possible limitation, though, we attempted to minimize this bias by searching 3 major electronic databases with no language restriction, while, some articles published in Chinese or other non-English languages may not appear in the international journal database, resulting in incomplete search.In conclusion, the results from this meta-analysis provide new evidence that AD is independently associated with an increased risk of stroke and MI after adjustment for established cardiovascular risk factors. Future studies on the effect of AD treatment and modifiable risk factor reduction on stroke and MI risk in AD patients are warranted.Min Yuan and Xu-Fang Xie conceived and designed the study. Min Yuan and Wen-Feng Cao searched the databases and checked these according to the eligible criteria and exclusion criteria. Xu-Fang Xie helped develop search strategies. Xiao-Mu Wu and Huang-Yan Zhou extracted the quantitative data. Min Yuan and Wen-Feng Cao analyzed the data. Min Yuan wrote the draft of the paper. All authors contributed in writing, reviewing, or revising the paper. Min Yuan and Xu-Fang Xie were the guarantors.


Background: Previous studies have investigated the association between a single marker of cerebral small vessel disease (SVD) and hemorrhagic transformation (HT). However, the effect of the total SVD burden on HT has not been evaluated yet. We aimed to investigate the association between the total SVD score and HT in ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease (RHD).Methods: Ischemic stroke patients with AF and/or RHD admitted within 7 days after onset were enrolled at two hospitals in China. The total SVD score was based on the presence of lacunes, extensive white matter hyperintensities, cerebral microbleeds, and moderate to severe enlarged perivascular spaces in the basal ganglia. One point was awarded for the presence of each marker, with the total SVD score ranging from 0 to 4 points. HT was assessed based on follow-up imaging scans during hospitalization and was classified according to the radiographic appearance and associated neurological deterioration.Results: Of 207 enrolled patients , 89 (43.0%) developed HT. The distribution of the total SVD score was significantly different between patients with and without HT in the univariate analysis (p = 0.04). After adjustment for confounders, a SVD score of 1 was independently associated with an increased risk of HT , while a SVD score ≥2 was inversely related to the occurrence of HT . These independent associations remained significant in the subgroups of hemorrhagic infarction and asymptomatic HT .Conclusions: In our study, the relationship between the total SVD score and HT was not linear, since the presence of only one marker of SVD was associated with an increased risk of HT, while the presence of two or more markers of SVD was a potential protective factor for HT. These results indicate the need to take the total SVD score into account, not only a single SVD marker, when assessing the risk of HT. Further studies with larger samples are required to validate these findings. Stroke is the second leading cause of death worldwide and the leading cause of death in China . CardioeCerebral small vessel disease (SVD) is an age-related disorder comprising various pathological processes and affecting the small blood vessels of the brain . Four maIn the present study, we aimed to investigate the association between the total SVD score and HT in ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease (RHD). We selected ischemic stroke patients with AF and/or RHD as the study cohort because they are treated most often with thrombolysis and anticoagulants, and because they show a higher incidence of HT than patients with other subtypes of stroke .We enrolled patients with ischemic stroke admitted to West China Hospital of Sichuan University  between October 2013 and December 2017, and to the People's Hospital of Deyang City  between October 2014 and July 2015. The inclusion criteria were (1) patients that experienced ischemic stroke confirmed by brain computed tomography (CT) or MRI who were admitted within 7 days after stroke onset, (2) an initial CT scan on admission and follow-up CT or MRI scans during hospitalization were performed, and (3) patients received an additional diagnosis of AF and/or RHD at discharge. Patients were excluded if the quality of brain scans was poor, making the assessment of SVD difficult, or if the relevant MRI sequences were unavailable, including T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR), and susceptibility-weighted imaging.Demographic and clinical information was extracted from medical databases, including age, sex, prior medical history , previous use of antithrombotic agents , smoking, alcohol consumption, stroke severity assessed by the National Institutes of Health Stroke Scale (NIHSS) on admission, blood pressure on admission, laboratory tests at the first visit, and treatments during hospitalization including antiplatelets, anticoagulants, and thrombolysis. Ischemic stroke was classified as cardioembolic, atherothrombotic, lacunar, or uncertain stroke based on the etiological classification defined by the Stroke Prevention in Atrial Fibrillation (SPAF) study .The study was approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University, and the protocol followed the local ethics criteria for human research. Written informed consent was obtained from all the participants or their legal representatives.Initial CT scans were performed within 24 h after admission, followed by scheduled MRI within 7 days after admission or repeated CT immediately whenever hemorrhage was suspected, such as in the case of headache or neurological deterioration. All CT examinations were performed using 64-section scanners  with 7-mm slice thickness. MRI images were obtained with a 1.5-T scanner  at the People's Hospital of Deyang City or a 3-T Siemens scanner at West China Hospital. MRI parameters have been previously described . All imaHT was defined as hemorrhage within the infarct territory or parenchyma hemorrhage outside the infarct zone that was detected on follow-up CT or MRI during hospitalization, but not on head CT on admission . In termThe total SVD score comprised four MRI markers of SVD . One point was awarded for the presence of each of the four markers, so scores could range from 0 to 4 , 10. Lact-test or the Mann–Whitney U-test for continuous variables and χ2 or Fisher's exact test for categorical variables. One-way analysis of variance (ANOVA), χ2, or the Kruskal–Wallis test was used to compare results among subgroups with different SVD scores. A multivariate logistic regression model was used to assess the independent association between the total SVD score and HT. The model included variables that were found to be potentially associated with HT in the univariate analyses (p < 0.10), as well as age, NIHSS score, blood glucose on admission, etiology of stroke, use of antiplatelets or anticoagulants, and use of thrombolysis, which are considered risk factors for HT .Results are presented as percentages, mean ± standard deviations (SDs), median with interquartile range (IQR), or odds ratios (ORs) with 95% confidence intervals (CIs), as appropriate. We compared the differences in the baseline characteristics between the groups of HT and non-HT using Student's s for HT , 26, 27.A total of 207 ischemic stroke patients were included in the study , of whomp < 0.001), sex (p = 0.04), prevalence of hypertension history (p < 0.001), NIHSS score (p = 0.004), systolic pressure (p = 0.002), and level of high-density lipoprotein (p = 0.01). However, they did not differ significantly in prevalence of diabetes mellitus, hyperlipidemia, smoking, alcohol consumption, use of antithrombotic drugs (antiplatelets and anticoagulants), or thrombolysis , a higher level of blood glucose (p = 0.004), and lower levels of total cholesterol and low-density lipoprotein (both p = 0.02) on admission compared to patients without HT. There was no significant difference in the use of antiplatelet drugs , while the proportion of patients treated with anticoagulants during hospitalization was lower in the HT group than in the non-HT group . Thrombolysis was more prevalent in the HT group than in the non-HT group, although the difference was not statistically significant .p = 0.04, p = 0.009), while HT was less common in patients with ≥2 points on the SVD score than in those with score <2 . Regarding the subtypes of HT, SVD score = 1 was always the most common, and there was a decrease in the proportion of patients with HT when the SVD score was higher than one point (p = 0.003), while SVD score ≥2 was a protective factor against HT  and less likely to present with CMBs together with other SVD markers . After adjusting for age, NIHSS score, blood glucose, total cholesterol, low-density lipoprotein, etiological classification, and treatment during hospitalization with thrombolytic, antiplatelet, and anticoagulant drugs, only CMBs remained significantly associated with HT .We further analyzed the association of each component of the SVD score with HT. When we analyzed each marker on its own, irrespective of the presence of the other three markers, none was significantly associated with HT  was inversely associated with the occurrence of HT.About 80% of ischemic stroke patients with AF and/or RHD had cerebral SVD in this study, with CMBs being the most common. Previous studies reported that cerebral SVD was present in ~60% of patients with mild stroke  and in aAlthough the total SVD score has been suggested to be associated with death and disability after stroke , 28, 29,Interestingly, our results implied that CMBs seemed to accelerate the development of HT, while the presence of other SVD markers may weaken the effect of CMBs on HT and even make CMBs exert protective rather than harmful effects. When we focused on individual markers irrespective of the presence of the other three markers, we found no significant association between each marker and risk of HT. This finding may partly explain why some studies about CMBs reported no relationship with HT , 40. TheOur study presents several limitations. First, subjects in this study were ischemic stroke patients with AF and/or RHD, who constitute a relatively specific population and may limit the generalizability of our findings to overall stroke patients. In addition, previous studies , 42 indiIn a cohort of ischemic stroke patients with AF and/or RHD, we investigated, for the first time, the association between the total SVD score and HT. The association between the total SVD score and HT was not linear, since the presence of only one marker of SVD (score = 1) was associated with an increased risk of HT, while the presence of two or more markers of SVD (score ≥2) was a protective factor against HT. These findings suggest a complex role for SVD in the development of HT, and further studies are required to clarify the underlying mechanisms. In addition, our results suggest the need to take into account the total SVD burden, not single SVD markers, when assessing the risk of HT.wyplmh@hotmail.com.The datasets for this manuscript are not publicly available because the data that support the findings of this study are available from the corresponding author upon reasonable request. Requests to access the datasets should be directed to ML, This study was carried out in accordance with the recommendations of the Biomedical Research Ethics Committee of West China Hospital, Sichuan University with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University.ML designed and supervised the study. CW, JLiu, and JLi collected the clinical data and analyzed the images. CW performed the statistical analysis and wrote the manuscript draft. JLiu critically revised the manuscript. All authors read and approved the final version submitted for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Background: The need for psychological therapies for psychosis has become apparent since long-term antipsychotic drug treatment has a range of adverse side effects, with moderate therapeutic effects at best.Aims: To investigate whether the psychotherapeutic approach, dialogue therapy (DT) is associated with improvements of symptoms and functioning beyond standard psychiatric treatment (ST) in both schizophrenia and other psychosis.Methods: A retrospective case-control design, comparing 54 patients with different psychoses who received DT with 54 patients in a control group receiving ST was carried out. The groups were matched on diagnosis, age, sex, and treatment start. Outcome measures were Global assessment of functioning (GAF) scores, medications at follow up, and hospital stays after completed outpatient treatment.Results: Mean time in treatment from inclusion to follow-up was 3 years and 5 months. At follow-up, GAF functioning (GAF-F) and GAF symptom (GAF-S) scores both were significantly higher in the DT group than the ST group. Effect sizes (Cohen's d) were large; 1.8 for GAF-S and 2.1 for GAF-F. At follow-up, the use of psychoactive drugs was significantly reduced despite a shorter time in psychotherapy in the DT group compared to the ST group. Days of hospitalizations after end of treatment in the study period were significantly reduced in both groups compared to the period before start of treatment.Conclusions: The findings from this exploratory study are consistent with the possibility that dialogue therapy may lead to improvements in symptoms and functioning compared to standard treatment in psychosis. Standard treatment (ST) for psychosis consists primarily of antipsychotics, hospitalization, social rehabilitation, and different types of supportive therapy –3. AntipCombinations of pharmacological and psychosocial treatments have demonstrated potential for recovery from psychosis , 11. A sDT is an individual, dialogue oriented psychotherapy that has been developed through the first author's clinical practice and collaboration with patients diagnosed with schizophrenia and other psychoses since the 1980's , 16. CenCreate a safe therapeutic relationshipCommunicate prospects of emotional knowledgeImpart enthusiasm, tune in and share languageBe genuine, show authenticity, and be responsiveNormalize and reduce psychotic mystery and fearCompliment improvements, provide hope, stimulate empowerment.DT consists of three treatment phases and is provided in 1-h weekly sessions over a course that lasts between 3 months and 3 years. In the first treatment phase, the focus is on aiding the patient out of the psychosis and awakening interest in participating in a common reality. The therapist emphasizes to create an atmosphere of safety and predictability, inclusion, hope and meaning, and to invite the patient to a co-creating treatment process characterized by dialogue and collaboration. The therapist expresses empathy, compassion, authentic commitment, and sensitive curiosity toward the patient's emotions, wordless signs, and utterings. The patient is invited to tell about problems she has and is assisted in reflecting on chaotic aspects of the psychosis. The patient is complimented on progress she has made and the therapist signals a strong belief in the patient's ability for change to restore health. These issues and aspects also constitute a longitudinal fundament in the therapy that frequently is returned to in subsequent phases. The central foci in the first phase can be summarized as follows:Maintain a safe and predictable therapeutic relationshipInclude all the patient's narratives, life-trauma, emotional utterances, ask questions, be curiousSee the whole human being, not only the illnessGet in between the symptoms (the illness) and the patient's healthy self-identityHighlight a process that helps restore a sense of selfExternalize and help the patients label their symptomsWithin the continued focus on establishing and maintaining a trustworthy, safe working alliance, central in the second treatment phase is to gradually include the patient in dialogue, reciprocity, and collaboration. The patient is helped to reach a greater understanding and regulation of her feelings and thoughts. The therapist is allowing for parts of the self that are dominated by the illness as well as healthy aspects of the self. By moving attention to the patient's healthy self-identity, the therapist uses emotions to stimulate the interactive process and emphasizes moments that can generate a breakthrough/splitting. This implies to help the patient in pushing symptoms aside to increase freedom and reciprocity in the dialogue and empower the patient's healthy identity. In these attempts to restore the self, the therapist personifies and visualizes symptoms to make them subjects of joint exploration, sees and compliments novel as well as previous achievements. Central foci in this phase are the following:Encourage independenceSearch for causes, free from burdenFind explanations, evolve new histories in re-authoring livesEmpower the patient's own qualitiesGive the patient tools from therapy and methodsSupport the journey back to normal life which includes job, educations or other activitiesThe third treatment phase is devoted to assist the patient back to normal life and functioning in the family and community. Independence is encouraged by increasing the scope of the dialogue and offering the patient to learn and gain insight from psychotherapeutic approaches and theories. The patient is offered assistance in searching for psychosocial explanations of symptoms in the past and present and to develop new ways of understanding. An emphasis is on strengthening the patient's belief in her own ability, resources and qualities to reestablish a meaningful life. Accordingly, various tools are provided to strengthen mental control and self-regulation to prevent relapse. This includes an emphasis on initiatives toward future work and education and other meaningful social activities. The foci of the third, final phase can be summarized as follows:For a more thorough description of DT see , 16]..16)].DT shares features with other psychotherapeutic approaches to psychosis but it also may have several unique features. First and foremost, DT has several meeting points with the Open Dialogue network model , 21. HowShared between DT and newer psychodynamic approaches for psychosis is the emphasis on thrust, causes, history and the therapeutic alliance. The psychodynamic approaches, however, more typically view psychosis, in particular schizophrenia, as biologically based illnesses that can be managed by learning practical coping strategies . These mCommon with DT, cognitive behavioral therapies (CBT) and metacognitive psychotherapies for psychosis typically emphasize simple and easy to understand interventions with a focus on the patient's current mental state –25. DT mWe have previously reported a larger improvement in symptoms and functioning, combined with a larger reduction in the use of psychopharmaca, in DT as compared to ordinary, standard treatment in 48 patients with a schizophrenia diagnoses  . In the This retrospective case-control study was conducted at the Psychiatric Outpatient Clinic (POC), Department of Psychiatry at Ålesund Hospital, Møre and Romsdal Health Trust. The hospital serves about 95,000 people from a geographical sector with both rural and urban areas. POC is a general treatment facility for all types of psychiatric conditions. Included in the study were patients enrolled to treatment at the outpatient clinic in the study period, which lasted from 1st of January 1991 to 1st of September 2008. Follow-up was defined as end of treatment or end of study period (which ever occured first). Follow up data were acquired a mean of 4 years and 1 month after treatment start. The study was approved by the National Research Ethical Committees (NEM) (2008/20) and by the Norwegian Social Science Data Services (NSD 20280). NEM and NSD approved the collection of anonymous data without patient consent. At any time point, treatment at POC is administered by an average of 25 clinicians. The majority are specialists in psychology or psychiatry, while a few are non-specialists in these disciplines, or psychiatric nurses, family therapists or clinical social workers. One person conducted DT psychotherapies (AH).Eligible for inclusion in the study were patients with a diagnosis in either of the following domains (ICD-10): Schizophrenia (F20.0-9), paranoid psychosis (F22.0-9), acute polymorph psychosis (F23.0-9), schizoaffective psychosis (F25.0-9), bipolar affective disorder (F31.0-9), and severe depression with psychotic symptoms (F32.3). No exclusion criteria were used.n = 54). The control group (n = 54) received ST and was selected from the total patient population with psychosis who were treated by other therapists than AH. Patients in the control group were matched to those in the intervention group on four variables in the following order of priority: 1. Diagnoses, 2. Month and year of therapy start, 3. Gender, and 4. Age. By matching the ST group on the month and year of therapy start, the two groups had the same amount of time to achieve therapeutic effects. Matching of patients was performed by an independent professional at the IT department at Ålesund Hospital, who had extensive experience from previous projects with similar mapping tasks. Characteristics of the intervention and control groups are summarized in All patients were first considered at an intake meeting at POC, and thereafter distributed to any of the about 25 therapists working at the unit in a coincidental, unsystematic (random) manner, with no consideration of any therapist characteristics . All patients treated with DT by the first author were included in the study, none were excluded. The control group was then matched to these patients. The intervention group received DT in addition to standard treatment  and consisted of all patients diagnosed with psychosis who were treated by AH  was the primary outcome measure. The secondary outcome measure was the number and dose of medications. Data also were gathered on number of admissions and days of hospitalization at psychiatric wards. All data were acquired from Electronic Patient Journals (EPJ) and paper journals by independent raters (psychiatrists).Different psychiatrists in charge made all the diagnosis by using the International Neuropsychiatric Interview (MINI/ MINI plus), Structured Clinical Interview for DSM Disorder (SCID) and Minnesota Multiphasic Personality Inventory (MMPI-2). In addition, the appropriate diagnoses were discussed in separate diagnostic meetings that included all involved personnel. The diagnoses were retrospectively confirmed by an independent psychiatrist using DSM-III-R, DSM-IV, and ICD-9/10 criteria.GAF is an observer-based continuous scale for the overall level of mental health/illness that ranges from 1 (most severe problems) to 100 . Used in this study was the split-version, with separate subscales for social, occupational and school functioning (GAF-F) and mental symptom burden (GAF-S) the last week . The varAll GAF scores were set in ordinary clinical care; however, they were decided upon as consensus ratings between at least two trained psychiatrists, a method documented to increase reliability . For theIn both treatment groups, psychopharmacological treatments were managed by different psychiatrists in charge. The prescribers did not use a shared decision making approach. We gathered information at baseline and follow up on any use of Antiepileptics (ATC code N03 A), antipsychotics (N05 A), anxiolytics (N05 B), hypnotics and sedatives (N05 C), and antidepressants (N06 A). Medication was sorted into the following subgroups: Low-dose Neuroleptics, High-dose Neuroleptics, Anxiolytics, Antidepressants, and Mood Stabilizers. All medications belonging to the same subgroup were added to derive at a summated dose for that subgroup. We also counted the total number of all psychoactive medications used.The psychiatrist who scored the use of medications also counted the number of hospital (inpatient) admissions, the total number of days spent in hospital, and treatment duration for outpatient treatments. These data were collected from the summary of each separate admission in the medical journals. There were no evaluations involved in these extractions and registrations. All data extractions were controlled by a collaborator. Hospital admissions and days spent in hospital were calculated for two time periods. First, a baseline measure that included all life time hospital stays prior to enrolment in outpatient treatment at POC. Second, a follow up measure for the time period after end of outpatient treatment at POC in the study period. Treatment duration was defined as months in outpatient treatments at POC during the study period. Information about the duration of outpatient treatment, number of days in hospital inpatient treatment and number of hospital admissions were extracted from the patients' journals. In DT, on average, one therapeutic session was provided each week for each patient.t-tests for GAF and age, Chi square test for gender, and Mann-Whitney U-tests for medications. Mann-Whitney U-tests were used to test differences in the number of hospitalizations and number of days in hospital before baseline and after treatment within each study group, and differences between the two study groups were analyzed with multiple regression analyses.Differences between patients in the two treatment conditions at baseline were tested with independent sample t-tests for GAF and Mann Whitney U-tests for medications. For GAF, we calculated effect size using Cohen's d. Next, we performed more detailed analyzes with control for covariates. For GAF, we used general linear modeling, with treatment group as fixed factor and, as covariates, diagnostic group , gender, age, number of days spent in hospital before treatment, and number of hospital stays before treatment. In these models we included as a covariate the interaction between treatment groups and diagnostic group, in order to investigate if an eventual superior effect of DT (or ST) was limited to just one of the two diagnostic groups. For medications, we used linear regression, with treatment condition, diagnostic group, gender, age, and the two noted hospitalization variables as predictors. In these analyses, we excluded duration of outpatient treatment as a covariate/ predictor since this variable was strongly correlated with treatment condition (shorter duration in DT). In multiple forward regression analyzes all factors with p < 0.20 were tested in the model.To investigate impacts of treatment group upon GAF and medications we focused both on scores at follow up and on changes from baseline to follow up. First, we used independent sample All analyses were performed in SPSS v. 23.0 for Windows .p = 0.003) and days of hospitalizations (p < 0.01) than the ST group. The patients in the DT group had shorter time (fewer months) in outpatient treatment during the study period compared to the ST group, median (min/max), 36 (1/132) vs. 72 (1/213) (p < 0.001).At baseline, there were no significant differences between the DT and ST groups in age or gender distribution , or in Gt(105) = 2.8, p = 0.007]. Compared to patients with schizophrenia, patients with other psychosis also had higher baseline scores on GAF-S,  and GAF-F  (left columns in p < 0.001) and fewer medications (p = 0.001)  = 9.80, p < 0.001] and GAF-F . Both GAF-S and GAF-F also changed differently in the two treatment groups from baseline to end of therapy, in favor of the DT group, with an increase of 44.9 vs. 12.8 for GAF-S,  and 43.7 vs. 15.0 for GAF-F, , respectively (d) favoring DT was 1.8 for GAF-S and 2.1 for GAF-F.At follow up, the DT and ST groups differed significantly on both GAF-S [mean 74.9 (15.2) vs. 47.5 (13.8), ectively . The effAt follow up there was no significant difference in GAF scores between the schizophrenia group and other psychoses.R2 = 0.47, B = 27.4, p < 001), and GAF-F . The interaction between treatment groups and diagnostic category  was not significant for any of the two GAF sub-dimensions, indicating a superior effect of DT over ST independent of diagnosis. No effects were seen for the covariates.The more detailed general linear model analysis for GAF scores at follow-up was significant for both GAF-S and GAF-F. A significant effect was seen for treatment groups upon both GAF-S , GAF-S at follow up , changes in GAF-S from baseline to follow up  and changes in GAF-F from baseline to follow up . Noteworthy, the interaction between treatment group and diagnostic category was not significant in any of the models, suggesting comparable effects of DT for patients with schizophrenia and for patients with other psychoses. See In each of the general linear models, with four variants of GAF as dependent variable, significant effects were seen only for treatment group; GAF-F at follow up . No interact effects were seen between treatment groups and diagnostic categories, indicating a larger improvement in GAF scores in DT as compared to ST both for patients with a schizophrenia diagnosis and patients with other diagnoses  and anxiolytics (p = 0.045), in addition to fewer number of drugs (p < 0.001). As can be seen in p = 0.001), antidepressants (p = 0.006), mood stabilizing medications (p = 0.004), and anxiolytics (p = 0.004), in addition to total number of drugs (p < 0.001).At follow up, patients in the DT as compared to the ST group used less low-dose antipsychotics .At follow up, the univariate regression analysis for the use of low-dose neuroleptics was significant, with effects for treatment group (less use in DT) and diagnostic group (less use in “other psychoses”). In multiple regression analyses, both factors were significant , anxiolytics  and mood stabilizing drugs  in univariate and multiple regression analyses were treatment group, with less use in the DT group. The only predictor for antidepressant dose was male sex . In multiple regression analyses the total number of drugs at the end of study was predicted by treatment group and diagnostic group , with less medication in the DT group and in other psychoses compared to schizophrenia.The only predictor for high dose neuroleptics . The changes in number of drugs from baseline to follow-up was also predicted by treatment group , with larger reduction in the DT group.The regression analysis for changes from baseline to follow-up in the use of medication was significant for low-dose neuroleptics, antidepressants, and other medications. The only significant predictor was belonging to the DT group (lower doses) . This was true both for low-dose and high-dose neuroleptics (p = 0.001 Mann-Whitney U-test). In logistic regression analyses, therapy group (DT) and schizophrenia diagnoses were significant predictors of not using medication , with more patients not using medication in the DT group and in other psychoses than schizophrenia. The same was true for not using low dose and high dose neuroleptics . The only predictor for not using mood stabilizing medication, anxiolytics, or other medications was belonging to the DT group .There was no significant difference between the treatment groups in number of patients without medication before start of treatment. However, after end of therapy, there was a significant difference, with fewer patients using medication in the DT group (p = 0.011). In multiple regression analyses, belonging to the DT group predicted more days in hospital after end of treatment . However, when one extreme outlier in the DT group was removed from the analyses, no effect remained for treatment group upon hospitalization days.During follow up, we observed more days of hospitalization in the DT group than the ST group  and the inability to meet normal requirements for work and studies.The larger improvements in GAF scores in DT could not be explained with increased medical treatments since medications rather were markedly reduced in DT as compared to ST across the treatment course. Nor could it be explained with longer duration of outpatient treatment, since DT on average had shorter duration than ST. The strong improvements in symptoms and functioning in DT compared to ST, combined with the reduction in use of medication, strengthen the assumption that the effective component included psychological changes based on a psychotherapeutic process.DT has an explicit focus on recovery from psychosis and aims both at symptom reduction through a therapeutic process oriented toward insight and self-regulation, and at helping the patient back to adequate functioning at home and in the society in general. The high GAF scores at follow up in the DT patients indicate that this goal was achieved.Studies of treatment effects indicate that people diagnosed with schizophrenia may benefit from acquiring insight into their internal states and the external circumstances of their illness. This may help them to see causal connections and develop histories about themselves that they better can live with , 33, conSince therapist factors may have a strong impact on outcome, a limitation is that DT involved a single therapist only; the apparent benefits of DT could alternatively reflect the particular skills and dedication of this therapist. At the same time, because only one therapist practiced DT (the founder of the model), adherence and fidelity checks have been less relevant to implement. On the other side, this has ensured a stable, comparable practice of DT for all its patients. However, the survey must be considered preliminary and exploratory, and controlled prospective studies that include more therapists providing DT are needed. Strengths include that all patients who received DT and fulfilled criteria for psychosis, were included in the study, and that the ST group was matched on several criteria to the DT group. However, the likely varied approaches in ST makes it difficult to know exactly what DT was compared to. A further limitation is that although GAF scores were set in consensus by at least two trained professionals, this was done in ordinary clinical care, with no independent scores set by researchers. Other weaknesses are that patients were not allocated to treatment groups using conventional randomization methods; the small size of the sample investigated; the limited range of outcome measures; and the dependence of the outcome measures on information in the clinical notes. Moreover, even if strengths include that all patients who received DT and fulfilled criteria for psychosis were included in this study, the limited range of outcome measures does not allow deepening the complexity of the sample, which includes the entire psychosis spectrum. We had no measure of the proportion of patients in ST who received psychoeducation and medication vs. medication only. Thus, suboptimal aspects of ST for some patients may have contributed to this group's worse outcome compared to DT.In this preliminary and exploratory study, compared to standard treatment, the psychotherapeutic approach Dialogue therapy was associated with improved functioning and reduced levels of general symptoms at follow up in both patients with schizophrenia and patients with other psychosis. The differences were seen in spite of reduced use of medication and shorter duration of therapy in DT. These promising findings for DT warrant subsequent controlled studies that include larger patient groups and more therapists in order to conclude about effects.The project was approved by the National Research Ethical Committees (NEM) (2008/20) and by the Norwegian Social Science Data Services (NSD 20280). NEM and NSD approved the collection of anonymous data without patient consent.AH, TH, and RF have made substantial contributions to conception, design, analysis, interpretation of data, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. AH, TH, EJ, and RF have been involved in interpreting the data and drafting the manuscript or revising it critically for important intellectual content. All authors read and approved the final version of the manuscript.AH has developed the new psychotherapeutic approach and published a book about the method. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Adenoid cystic carcinoma of the trachea is a rare tumor, characterized by slow growth and low rate of local and distant metastasis. When achievable, complete surgical resection represents the optimal treatment approach, with the highest results in terms of overall survival. Radiation therapy is a reasonable alternative in cases of inoperable disease.We report a case of an 82-year-old white man affected by primary adenoid cystic carcinoma of the trachea, treated with debulking surgery and radiotherapy on the residual disease.A three-dimensional conformal radiation therapy was conducted. The total dose amounted to 70 Gy, administered in 35 fractions of 2 Gy. The medium doses given to the esophagus and lungs were 23 Gy and 4.2 Gy respectively. The maximum dose delivered to the spinal cord was 31 Gy with satisfactory results in terms of local control of the disease.A combined approach of surgical resection followed by radiotherapy on the residual disease provided an excellent result in terms of disease control, quality of life, and overall survival in a patient with locally advanced tracheal adenoid cystic carcinoma. Primary tracheal malignant tumors represent 0.1 to 0.4% of all malignant neoplastic diseases and their incidence is approximately 0.1 per 100,000 per year. Malignant tumors of the trachea tend to occur more often in the adult population than in children, but the distribution between the two sexes is almost the same.Primary adenoid cystic carcinoma (ACC) of the trachea and squamous cell carcinoma (SCC) are the most frequent histological types of tracheal malignant tumors, accounting for approximately two thirds of adult primary tracheal tumors. The other histological classes are very rare and include sarcoma, melanoma, mucoepidermoid carcinoma, lymphoma, and non-squamous bronchogenic carcinoma.ACC seems not to be related to tobacco smoking, and its prognosis is generally better than SCC, which progresses faster and frequently metastasizes. In contrast, only 10% of patients affected by ACC present with locoregional or distant metastases. The main growth patterns of tracheal ACC documented in histological samples are tubular, solid, and cribriform, the latter is the most frequently observed.Local recurrences are not uncommon in ACC, but they are frequently late. Radical surgery is related to the best outcomes in overall survival; in unresectable tumors, radiotherapy ensures satisfactory results in terms of local control of the disease, and is adequate to treat residual disease after surgery , 2.Here we report a case of such rare pathology that we managed it with a combinatorial strategy of surgery and radiotherapy which allowed adequate disease control.We report a case of an 82-year-old white man, who never smoked tobacco or consumed alcohol, who presented with a 3-month history of tracheitis and dysphonia. His past medical history was characterized by multiple myeloma, Gilbert syndrome, chronic obstructive pulmonary disease (COPD) treated with bronchodilators, cardiac arrhythmia treated with amiodarone, and arterial hypertension treated with angiotensin-converting enzyme (ACE) inhibitors.On arrival, his physical signs were as follows: oriented, collaborating, and autonomous walking; a neurological examination showed no abnormalities; blood pressure 130/85 mmHg and pulse 80 beats/minute; no fever; and regular bowel function and diuresis. Routine laboratory tests were performed, including complete blood count, renal and liver function tests, and electrolytes. All the results of the laboratory tests were almost within normal range.A frontal and lateral chest radiograph was performed as first imaging procedure: it showed prominent pulmonary hila and a reduction of vascular marking, but no nodular lesions or neoformations were documented. Therefore he underwent a total body computed tomography (CT) scan without contrast, due to the multiple myeloma, which revealed the presence of massive hyperdense solid tissue in the mid-proximal trachea, protruding into the lumen. This neoformation determined compression and narrowing at the level of the anterior-lateral wall of the right portion of his esophagus.Thus, he underwent a bronchoscopy that confirmed tracheal lumen narrowing between the first and fifth tracheal ring. A biopsy specimen of the lesion revealed a salivary gland-type neoplasm, showing a moderate degree of aggressiveness, with the characteristics of ACC Fig. a, b.Fig.Due to the rarity of the neoplasm, with less than two cases in 1 year in our institute, a review of the literature was made. A multidisciplinary team of oncologists, radiologists, radiotherapists, and surgeons decided to treat our patient with an endotracheal debulking surgical excision of the lesion followed by radiotherapy.18F-fluorodeoxyglucose (18-FDG) uptake /CT scan was performed: a residual solid tissue with a maximum diameter of 46 mm was evident in the middle mediastinum, infiltrating the upper middle third of his trachea and showing strong ake Fig. a. A threAfter 1 year of follow-up, no early or late toxicities related to the radiotherapy were observed: there was no dysphagia or weight loss.PET-CT scans performed after 6 and 12 months of follow-up showed a complete response to the radiotherapy, with only a focal increased uptake at the level of superior pulmonary lobes, which referred to post-radiotherapy inflammation  treatment.A better prognosis is mainly related to the feasibility of complete resection and to the absence of metastasis. However, symptoms such as wheezing, tracheitis, hemoptysis, and stridency are often unspecific and late. Lymph nodal involvement has not been associated with a worse prognosis , 4.The overall survival at 5 years of tracheal ACC is approximately 30% with a reduction to 18% in cases of extratracheal extension. In cases of intraluminal disease, all the studies shows a 5-year overall survival rate of 50% [The optimal treatment approach for ACC consists of radical surgical resection with negative margins achievement and reconstruction . SurgicaWhen complete resection cannot be achieved, postoperative radiotherapy seems to have a statistically significant impact on survival –8. ACC oAlthough there is not an accepted standard, usually the dosage of postoperative radiotherapy is 60 Gy . Endotracheal brachytherapy can be used to give a boost on the primary tumor or to treat advanced stages with palliative intent .In cases of inoperable disease, radiotherapy alone can reach a sufficient local control of the disease, but it does not give results comparable to those of surgery. Palliation can be obtained with several procedures, such as electrocoagulation, cryotherapy, photodynamic therapy, or with stents, above all in cases of severe airway obstruction.et al. [Many studies are available in the scientific literature about the employment of radiotherapy in ACC Table . Maziak et al.  publisheet al. .Table 1Set al. [Kanematsu et al.  in a retet al. [Le Pechoux et al.  proved aet al. [Regnard et al.  conducteet al. [Bonner Millar et al.  comparedet al. [Bittner et al.  publisheet al. [Radiotherapy should always be performed in order to cover the entire tumor bed and to spare the surrounding normal tissues. In cases of treatment of tracheal tumors, preventing near structures  from accidental irradiation is particularly important to limit side effects and late complications. Alongi et al.  in a casIn conclusion, due to the rarity of the disease and thus the lack of randomized clinical trials, there is not yet a standardized therapeutic approach to tracheal ACC. In our experience, considering the slow tumor growth and despite our patient’s short follow-up, the combinatorial strategy of a debulking surgery followed by postoperative radiotherapy successfully achieved adequate disease control, suggesting it would be considered in the treatment option of locally advanced ACC of the trachea.