Patient’s Outcome Expectancies and Treatment Outcome Influence of Patient’s Outcome Expectancies on Symptom Improvement and Drop-out in Interpersonal Psychotherapy and Cognitive Therapy for adult depression

This study aims to explore the influence of expectations on treatment outcome of depressed patients following Interpersonal Psychotherapy or Cognitive Therapy. Patients’ baseline outcome expectations might influence post-treatment symptom improvement and dropout during treatment. Outcome expectations are hypothesized to influence the level of symptom improvement and the drop-out risk. The current study is based on data collected in a large RCT in which participants are assigned to either Cognitive Psychotherapy (N=76) or Interpersonal Psychotherapy (N=75) in order to be treated for a primary depressive episode. The Outcome Expectations Questionnaire was conducted at baseline, followed by a 7 months intervention phase. The primary outcome measurement is symptom improvement, which is the difference in symptoms at 7 months and at baseline. The second outcome measurement, drop-out, is the percentage participants that stop the treatment after following less than 12 session, while still having complains. The relationship between outcome expectations and symptom improvement and between outcome expectations and drop-out were analyzed separately. Contradictory to the hypothesis, the data did not show a significant relationship between outcome expectations and symptom improvement or drop-out. These findings implicate that patients with low outcome expectations have the same symptom improvement and risk to drop-out of the treatment as patients with high expectations. Other studies support this findings. However, more well-designed major studies are needed in order to gather more evidence-based information on the influence of outcome expectations on treatment outcome

Does a reduction in alcohol use by Dutch high school students relate to higher use of tobacco and cannabis?

Background: Substance use of adolescents was investigated in a region around Amsterdam, the Netherlands, in the period 2005-2009. The study was intended to find out to what extent behaviour related to different substances are interrelated and how trends develop in different subgroups. Methods: Two cross-sectional surveys were conducted among Dutch students in the second and fourth year of secondary school, aged 13-16 [n = 1,854 in 2005; n = 2,088 in 2009] by making use of an online questionnaire including questions about alcohol consumption, tobacco use (smoking behaviour) and cannabis use. Two educational levels were included. Results: Decreases in alcohol consumption, tobacco and cannabis use were found between 2005 and 2009. The strongest decline was seen in alcohol consumption. Last month drinking decreased from 61.8 % in 2005 to 36.5 % in 2009. Last month binge drinking decreased from 38.7 % in 2005 to 24.0 % in 2009. Reduced alcohol consumption was found among boys and girls, for all ages and in both educational levels. Changes were strongest among 13-year-olds. Weekly or daily smoking declined between 2005 and 2009 among 13-year-olds, girls and students in the lower schooling level. Last month cannabis use decreased among girls and students in the higher schooling level. In both 2005 and 2009 clustering with alcohol consumption was found for the use of other substances. Conclusions: Between 2005 and 2009 alcohol consumption strongly decreased among high school students. This may be due to the national prevention campaign which in the same period highlighted the importance of not drinking before the age of 16. The decrease in smoking and cannabis use between 2005 and 2009 may be due to clustering with alcohol consumption. A reduction in the use of alcohol in adolescence did not lead to replacement by tobacco or cannabis use

Assessment of IgG-Fc glycosylation from individual RhD-specific B cell clones reveals regulation at clonal rather than clonotypic level

The type and strength of effector functions mediated by immunoglobulin G (IgG) antibodies rely on the subclass and the composition of the N297 glycan. Glycosylation analysis of both bulk and antigen-specific human IgG has revealed a marked diversity of the glycosylation signatures, including highly dynamic patterns as well as long-term stability of profiles, yet information on how individual B cell clones would contribute to this diversity has hitherto been lacking. Here, we assessed whether clonally related B cells share N297 glycosylation patterns of their secreted IgG. We differentiated single antigen-specific peripheral IgG+ memory B cells into antibody-secreting cells and analysed Fc glycosylation of secreted IgG. Furthermore, we sequenced the variable region of their heavy chain, which allowed the grouping of the clones into clonotypes. We found highly diverse glycosylation patterns of culture-derived IgG, which, to some degree, mimicked the glycosylation of plasma IgG. Each B cell clone secreted IgG with a mixture of different Fc glycosylation patterns. The majority of clones produced fully fucosylated IgG. B cells producing afucosylated IgG were scattered across different clonotypes. In contrast, the remaining glycosylation traits were, in general, more uniform. These results indicate IgG-Fc fucosylation to be regulated at the single-clone level, whereas the regulation of other glycosylation traits most likely occurs at a clonotypic or systemic level. The discrepancies between plasma IgG and culture-derived IgG, could be caused by the origin of the B cells analysed, clonal dominance or factors from the culture system, which need to be addressed in future studies. Proteomic

Declining Hepatitis C Virus (HCV) Incidence in Dutch Human Immunodeficiency Virus-Positive Men Who Have Sex With Men After Unrestricted Access to HCV Therapy

Background Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)–positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Methods Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recru

Expanding the clinical and genetic spectrum of ALPK3 variants: phenotypes identified in pediatric cardiomyopathy patients and adults with heterozygous variants

Introduction Biallelic damaging variants in ALPK3, encoding alpha-protein kinase 3, cause pediatric-onset cardiomyopathy with manifestations that are incompletely defined.Methods and Results We analyzed clinical manifestations of damaging biallelic ALPK3 variants in 19 pediatric patients, including nine previously published cases. Among these, 11 loss-of-function (LoF) variants, seven compound LoF and deleterious missense variants, and one homozygous deleterious missense variant were identified. Among 18 live-born patients, 8 exhibited neonatal dilated cardiomyopathy (44.4%; 95% CI: 21.5%-69.2%) that subsequently transitioned into ventricular hypertrophy. The majority of patients had extracardiac phenotypes, including contractures, scoliosis, cleft palate, and facial dysmorphisms. We observed no association between variant type or location, disease severity, and/or extracardiac manifestations. Myocardial histopathology showed focal cardiomyocyte hypertrophy, subendocardial fibroelastosis in patients under 4 years of age, and myofibrillar disarray in adults.Rare heterozygous ALPK3 variants were also assessed in adult-onset cardiomyopathy patients. Among 1548 Dutch patients referred for initial genetic analyses, we identified 39 individuals with rare heterozygous ALPK3 variants (2.5%; 95% CI: 1.8%3.4%), including 26 missense and 10 LoF variants. Among 149 U.S. patients without pathogenic variants in 83 cardiomyopathy-related genes, we identified six missense and nine LoF ALPK3 variants (10.1%; 95% CI: 5.7%-1 6.1%). LoF ALPK3 variants were increased in comparison to matched controls (Dutch cohort, P = 1.6x10(-5); U.S. cohort, P = 2.2x10(-13)).Conclusion Biallelic damaging ALPK3 variants cause pediatric cardiomyopathy manifested by DCM transitioning to hypertrophy, often with poor contractile function. Additional extracardiac features occur in most patients, including musculoskeletal abnormalities and cleft palate. Heterozygous LoF ALPK3 variants are enriched in adults with cardiomyopathy and may contribute to their cardiomyopathy. Adults with ALPK3 LoF variants therefore warrant evaluations for cardiomyopathy.Genetics of disease, diagnosis and treatmen

Reversal reaction in borderline leprosy is associated with a polarized shift to type 1-like Mycobacterium leprae T cell reactivity in lesional skin. A follow-up study

Borderline leprosy patients often undergo acute changes in immune reactivity that manifest as reversal reaction (RR) in the course of the disease. RR is associated with an exacerbated local delayed-type cellular immune response to Mycobacterium leprae and is responsible for severe tissue damage. We investigated whether RR episodes are associated with a change in T cell subsets in the lesional skin with regard to their cytokine secretion profiles. M. leprae-responsive T cell lines and thereafter T cell clones (TCC) were generated from the lesional skin of seven untreated borderline leprosy patients (with or without RR) and again from three of these patients experiencing RR during treatment. The phenotypes of the M. leprae-responsive TCC were either CD4+, CD8+, CD4-/CD8+/TCR gammadelta+, or CD4-/CD8-/TCR gammadelta+, although most of them were CD4+. Regardless of the clinical status of the untreated patients, a major subset of the M. leprae-responsive TCC was type 0-like and produced both IFN-gamma and IL-4. Interestingly, in all three patients who experienced a (re)occurrence of RR during treatment after the first analysis, a clear shift to polarized IFN-gamma production by the M. leprae-responsive TCC (type 1-like) was observed. This shift in T cell subsets was also reflected in the observed decrease in serum IgG and IgM levels of the same patients during RR. These finding indicate that CD4+ M. leprae-responsive T cells with a polarized type 1-like phenotype might be responsible for the immune-mediated tissue damage occurring during R