Baseline MELD score predicts hepatic decompensation during antiviral therapy in patients with chronic hepatitis C and advanced cirrhosis

Background and Aims: In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV) infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined. Methods: In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18±2.72) were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240weeks, ±SD 136weeks). Results: Eighteen patients (26.5%) achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001). Conclusions: Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis

Incontinence in persons with tuberous sclerosis complex

Aims Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by a mutation in the TSC1 or TSC2 gene with a broad spectrum of physical and psychological manifestations. The aim of the study was to examine incontinence, psychological problems, and adaptive behavior skills in patients with TSC. Methods Through a worldwide TSC support group, 26 children (4‐17 years) and 15 adults (18‐50 years) with TSC were recruited (38.1% male, mean age 16.4 years). Parents or care‐givers completed the Developmental Behavior Checklist (DBC), the Parental Questionnaire: Enuresis/urinary Incontinence, and the Vineland Adaptive Behavior Scales (3rd edition). Results A total of 60.0% of the participants had nocturnal enuresis (NE), 51.3% daytime urinary incontinence (DUI) and 52.4% fecal incontinence (FI). 65.4% of children and 50.0% of adults had a clinically relevant DBC score. Psychological symptoms were associated with at least one subtype of incontinence. The mean adaptive behavior composite (ABC) score of the patients was 57.2 (SD = 26.1), with 38.1% in the average or below‐average range (IQ >70), 26.2% with a mild, 11.9% with a moderate and 23.8% with a severe/profound intellectual disability. The incontinence rate was significantly higher in the groups with a lower ABC score. Conclusion A substantial proportion of patients with TSC are affected by incontinence and psychological symptoms. Incontinence was higher in persons with lower adaptive skills and those with at least one type of incontinence showed a significantly higher DBC score. As incontinence and psychological problems affect daily functioning and well‐being, assessment, and treatment are recommended

The PI3K∂-Selective Inhibitor Idelalisib Induces T- and NK-Cell Dysfunction Independently of B-Cell Malignancy-Associated Immunosuppression

B-cell receptors, multiple receptor tyrosine kinases, and downstream effectors are constitutively active in chronic lymphocytic leukemia (CLL) B cells. Activation of these pathways results in resistance to apoptosis and enhanced survival of the leukemic cells. Idelalisib is a highly selective inhibitor of the PI3K p110∂ isoform and is approved for the treatment of CLL in patients with relapsed/refractory disease or in those harboring 17p deletions or tp53 mutations. Despite the initial excitement centered around high response rates in clinical trials of idelalisib, its therapeutic success has been hindered by the incidence of severe opportunistic infections. To examine the potential contribution of idelalisib to the increased risk of infection, we investigated the effects of idelalisib on the immune cell compartments of healthy donors (HDs) and CLL patients. PI3K∂ blockade by idelalisib reduced the expression levels of inhibitory checkpoint molecules in T cells isolated from both HDs and CLL patients. In addition, the presence of idelalisib in cultures significantly decreased T-cell-mediated cytotoxicity and granzyme B secretion, as well as cytokine secretion levels in both cohorts. Furthermore, idelalisib reduced the proliferation and cytotoxicity of HD NK cells. Collectively, our data demonstrate that both human T and NK cells are highly sensitive to PI3K∂ inhibition. Idelalisib interfered with the functions of T and NK cell cells from both HDs and CLL patients. Therefore, idelalisib might contribute to an increased risk of infections regardless of the underlying B-cell malignancy

Patient experience and satisfaction with symptomatic Faecal Immunochemical Testing: An explanatory sequential mixed-methods evaluation

Background: Recent evidence suggests that faecal immunochemical testing (FIT) can rule out colorectal cancer in symptomatic adults. To date, there is little research exploring experiences of FIT for this population. Aim: To explore patient experience and satisfaction with FIT in an ‘early adopter’ site in England. Design: We used an explanatory sequential mixed-methods approach combining mailed quantitative surveys with semi-structured telephone interviews. Methods: Multivariate logistic regression was used to analyse quantitative data. Thematic analysis was used to assess qualitative transcripts. Results: The survey had 260 respondents and found satisfaction with FIT was high (88.7%). Compared with test satisfaction, the proportion of respondents satisfied with GP consultation, and how they received their results, was lower (74.4% and 76.2%, respectively). Multivariate analysis showed increased area-level deprivation and not receiving an explanation of the purpose of the test were associated with lower satisfaction with GP consultation (both P-values&lt;0.05), while increased area-level deprivation and not receiving results from the GP were associated with lower satisfaction with receiving results (both P-values&lt;0.05). Interviews with respondents (n=20) helped explain the quantitative results. They revealed that “not knowing the purpose of the test” caused “anxiety” and “confusion”, which led to dissatisfaction. “Not receiving results from GP” was considered “unacceptable”, as this left patients with a “niggling doubt” and lack of diagnosis, or assurance that they did not have cancer. Conclusion: Patient satisfaction with symptomatic FIT is high. Efforts to improve satisfaction should focus on ensuring patients understand the purpose of the test and always receive their test results

Skill set or mind set? Associations between health literacy, patient activation and health.

OBJECTIVE: There is ongoing debate on whether health literacy represents a skill-based construct for health self-management, or if it also more broadly captures personal 'activation' or motivation to manage health. This research examines 1) the association between patient activation and health literacy as they are most commonly measured and 2) the independent and combined associations of patient activation and health literacy skills with physical and mental health. METHODS: A secondary analysis of baseline cross-sectional data from the LitCog cohort of older adults was used. Participants (n = 697) were recruited from multiple US-based health centers. During structured face-to-face interviews, participants completed the Test of Functional Health Literacy in Adults (TOFHLA), the Patient Activation Measure (PAM), the SF-36 physical health summary subscale, and Patient Reported Outcomes Measurement Information Service (PROMIS) short form subscales for depression and anxiety. RESULTS: The relationship between health literacy and patient activation was weak, but significant (r = 0.11, p<0.01). In models adjusted for participant characteristics, lower health literacy was associated with worse physical health (β = 0.13, p<0.001) and depression (β = -0.16, p<0.001). Lower patient activation was associated with worse physical health (β = 0.19, p<0.001), depression (β = -0.27, p<0.001) and anxiety (β-0.24, p<0.001). CONCLUSIONS: The most common measures of health literacy and patient activation are weakly correlated with each other, but also independently correlated with health outcomes. This suggests health literacy represents a distinct skill-based construct, supporting the Institute of Medicine's definition. Deficits in either construct could be useful targets for behavioral intervention

Effect of head shape variations among individuals on the EEG/MEG forward and inverse problems

We study the effect of the head shape variations on the EEG/magnetoencephalography (MEG) forward and inverse problems. We build a random head model such that each sample represents the head shape of a different individual and solve the forward problem assuming this random head model, using a polynomial chaos expansion. The random solution of the forward problem is then used to quantify the effect of the geometry when the inverse problem is solved with a standard head model. The results derived with this approach are valid for a continuous family of head models, rather than just for a set of cases. The random model consists of three random surfaces that define layers of different electric conductivity, and we built an example based on a set of 30 deterministic models from adults. Our results show that for a dipolar source model, the effect of the head shape variations on the EEG/MEG inverse problem due to the random head model is slightly larger than the effect of the electronic noise present in the sensors. The variations in the EEG inverse problem solutions are due to the variations in the shape of the volume conductor, while the variations in the MEG inverse problem solutions, larger than the EEG ones, are caused mainly by the variations of the absolute position of the sources in a coordinate system based on anatomical landmarks, in which the magnetometers have a fixed position.Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señale

Petersburger Erklärung: Anstöße für eine zukunftsgerichtete Arbeitsmarktpolitik

Anläßlich eines Symposiums, veranstaltet vom neu gegründeten Forschungsinstitut zur Zukunft der Arbeit (IZA) in Bonn, legten sechs Ökonomen in einer „Petersberger Erklärung' Thesen zur Arbeitsmarktpolitik vor. Nachfolgend der Wortlaut der Erklärung --

Gründungsaufruf und Gründung: Brevitas – Gesellschaft zur Erforschung vormoderner Kleinepik

PD

Welche Vorschulkinder profitieren nicht von einer mathematischen Förderung?

Hintergrund: Vorschulische Fördermaßnahmen können die Lernentwicklung bis in die Grundschule positiv beeinflussen. Die vorliegende Studie untersucht die Gründe, warum einige Kinder nicht von einer vorschulischen mathematischen Förderung profitieren (Non-Responder). Methode: Maße der Intelligenz, des Arbeitsgedächtnisses, der visuell-räumlichen Wahrnehmung, der Aufmerksamkeit und der Sprache sowie Elterneinschätzungen externalisierender Verhaltensauffälligkeiten und Hyperaktivität wurden vor einer Förderung bei 40 fünfjährigen Kindern mit einem Risiko für die Entwicklung einer Rechenstörung erhoben. Ergebnisse: Die Non-Responder ( n = 15) unterschieden sich bedeutsam von den Respondern ( n = 25) in den sprachlichen Variablen (verbale Intelligenz, phonologische Bewusstheit und expressive Sprache). Eine schrittweise Diskriminanzanalyse identifizierte die verbale Intelligenz als signifikanten Prädiktor und konnte 73% der Non-Responder korrekt klassifizieren. Tendenziell zeigten Non-Responder auch in weiteren domänenunspezifischen Variablen geringere Leistungen sowie ein höheres Ausmaß an externalisierenden Verhaltensauffälligkeiten. Die Prognose der Non-Responder hinsichtlich ihrer Rechenleistungen bis in die 3. Klasse fällt schlechter aus als die der Responder. Diskussion: Eine rein mathematische vorschulische Förderung erscheint für Kinder mit geringen Leistungen im sprachlichen Bereich nicht ausreichend. Für diese Kinder sind ergänzende Maßnahmen notwendig

Paediatric refugees from Ukraine: guidance for health care providers

BACKGROUND: With the invasion of Ukraine by the Russian Army in February 2022, refugees, the majority of whom are women and children, started fleeing the war to neighbouring countries. Even before the current escalation, the conflict in the eastern part of Ukraine has led to the internal displacement of more than 200,000 children, and many others have experienced attacks, e.g. on schools. This inevitably leads to limitations in health care delivery. During transit, overcrowding, poor shelter and vulnerability may further put refugees at increased risk for infectious diseases. This consensus document aims to provide information and guidance regarding health issues that paediatricians and general practitioners may face when caring for Ukrainian children. METHODS: Members of the Migrant Health Reference Group of Paediatrics Switzerland and the Paediatric Infectious Disease Group in Switzerland developed this recommendation between March and April 2022 in a modified Delphi process. RESULTS: A total of 50 recommendations were agreed on with a ≥80% consensus. These include the following topics: i) general aspects, including interpreter services, urgent health needs, personal history and general check-ups; ii) mental health, including how to search for signs of psychological distress without going into traumatic details; iii) vaccinations, including recommendations for evaluation and catch-up; iv) screening for tuberculosis, human immunodeficiency virus, and hepatitis B and C; and v) providing age-appropriate preventive and health service information. CONCLUSION: This document provides current evidence and guidance when caring for paediatric refugees from Ukraine. The recommendations focus on Switzerland but may well be used in other countries. These are based on current evidence and may need to be adapted to individual situations and once further evidence becomes available