The Cost-Effectiveness of the Kiva Antibullying Program: Results from a Decision-Analytic Model

Bullying causes substantial suffering for children and adolescents. A number of bullying prevention programs have been advocated as effective methods for counteracting school bullying. However, there is a lack of economic evaluations of bullying prevention programs assessing the “value for money.” The aim of this study was to assess the cost-effectiveness of the Finnish bullying prevention program KiVa in comparison to “status quo” (treatment as usual) in a Swedish elementary school setting (grades 1 to 9). The cost-effectiveness analysis was carried out using a payer perspective based on a Markov cohort model. The costs of the program were measured in Swedish kronor and Euros, and the benefits were measured using two different metrics: (1) the number of victim-free years and (2) the number of quality adjusted life years (QALYs). Data on costs, probability transitions, and health-related quality of life measures were retrieved from published literature. Deterministic and probabilistic sensitivity analyses were carried out to establish the uncertainty of the cost-effectiveness results. The base-case analysis indicated that KiVa leads to an increased cost of €829 for a gain of 0.47 victim-free years per student. In terms of the cost per gained QALY, the results indicated a base-case estimate of €13,823, which may be seen as cost-effective given that it is lower than the typically accepted threshold value in Swedish health policy of around €50,000. Further research is needed to confirm the conclusions of this study, especially regarding the treatment effects of KiVa in different school contexts.     

Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease

Background and aim: Moderate alcohol consumption has been associated with a lower risk of disease severity in non-alcoholic fatty liver disease (NAFLD). It is unclear if this reflects current or lifetime drinking, or can be attributed to confounders such as diet and exercise. We evaluated the impact of lifetime alcohol consumption on fibrosis severity in NAFLD.

Methods: We prospectively enrolled 120 subjects with biopsy-proven NAFLD and through detailed questionnaires examined lifetime alcohol consumption, diet and physical activity. Main outcome measures were odds ratios (OR) for fibrosis stage, calculated through ordinal regression after adjustment for body mass index, diabetes mellitus type 2, smoking and age at biopsy. A biomarker for recent alcohol consumption, phosphatidyl ethanol (PEth) was sampled.

Results: An increase in median weekly alcohol consumption to a maximum of 13 drinks per week was associated with lower fibrosis stage (adjusted OR for each incremental unit, 0.86; 95% CI, 0.76–0.97; p?=?.017). The lowest risk for fibrosis was found with the lowes`t odds seen in the top quartile of alcohol consumption (aOR 0.23; 95% CI 0.08–0.66; p?=?.006). Adding soft drink and coffee consumptions, and physical activity to the model did not change the estimates. Subjects with PEth ≥0.3?μmol/L had higher ORs for a higher fibrosis stage (aOR 2.77; 95% CI 1.01–7.59; p?=?.047).

Conclusion: Lifetime alcohol consumption with up to 13 units per week is associated with lower fibrosis stage in NAFLD. Elevated PEth is associated with higher stages of fibrosis.     

Interleukin-1 system gene polymorphisms are associated with fat mass in young men

CONTEXT: There is growing evidence for interactions between the regulation of body fat and the immune system. Studies of knockout mice indicate that IL-1 has an antiobesity effect. OBJECTIVE: The objective of the study was to investigate our hypothesis that common polymorphisms of the IL-1 system, which are associated with IL-1 activity, also are associated with fat mass. DESIGN, SETTING, AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-yr-old men (n = 1068), mostly Caucasian, from the Gothenburg area (Sweden). Three different polymorphisms, IL-1beta +3953 C/T, IL-1beta-31 T/C, and IL-1 receptor antagonist (IL-1RN) variable number tandem repeat of 86 bp, were investigated in relation to body fat mass. MAIN OUTCOME MEASURE: The main outcome measures were genotype distributions and their association with body fat mass in different compartments, measured with dual-energy x-ray absorptiometry. RESULTS: Carriers of the T variant (CT and TT) of the +3953 C to T (F(T) = 0.25) IL-1beta gene polymorphism had significantly lower total fat mass (P = 0.013) and also significantly reduced arm, leg, and trunk fat, compared with CC individuals. IL-1RN*2 carriers with two repeats of the IL-1RN variable number tandem repeat polymorphism had increased total fat (P = 0.036), serum leptin, and fat of trunk and arm as well as serum levels of IL-1RN and IL-1RN production ex vivo. The IL-1beta-31 polymorphism did not correlate with the fat measurements. CONCLUSIONS: The IL-1 system, recently shown to affect fat mass in experimental animals, contains gene polymorphisms that are associated with fat mass in young men.     

Feasibility of noncontact piezoelectric detection of photoacoustic signals in tissue-mimicking phantoms

The feasibility of air-coupled ultrasound transducers to detect laser-induced ultrasound from artificial blood vessels embedded in an optically scattering phantom is demonstrated. These air-coupled transducers allow new applications in biomedical photoacoustic imaging where contact with tissue is not preferred. One promising application of such transducers is the addition of photoacoustic imaging to the regular x-ray mammographic screening procedure.     

Stromal cells direct local differentiation of regulatory dendritic cells

CD11c(hi) dendritic cells (DC) play an essential role during the initiation of cell-mediated immunity. Recently, CD11c(lo)CD45RB(hi) DC with regulatory properties have been described. However, the origins of regulatory DC are poorly understood. Here, we show that spleen-derived stromal cells promote selective development of CD11c(lo)CD45RB(+) IL-10-producing regulatory DC from lineage-negative c-kit(+) progenitor cells. These DC have the capacity to suppress T cell responses and induce IL-10-producing regulatory T cells in vitro and to induce antigen-specific tolerance in vivo. Furthermore, stromal cells from mice infected with Leishmania donovani more effectively supported differentiation of these highly potent regulatory DC. The ability of tissue stromal cells to direct the development of DC with a regulatory phenotype thus provides a new mechanism for local immune regulation.     

Extracellular survivin up-regulates adhesion molecules on the surface of leukocytes changing their reactivity pattern

Rheumatoid arthritis (RA) is an autoimmune disease with joints as a principal target of inflammation. We have shown recently that the extracellular expression of the antiapoptotic protein survivin is associated with a destructive course of RA. Here, we address the potential impact of extracellular survivin on peripheral blood leukocytes (PBL). The binding of survivin to the surface of human PBL as well as the expression of adhesion molecules were assessed by FACS. The expression of adhesion molecules on leukocytes as a function of circulating survivin was analyzed in blood of 24 patients with RA and compared with eight healthy individuals. We show that extracellular survivin expresses immunomodulatory properties. It binds to the surface of the majority of granulocytes and a significant part of lymphocytes and monocytes inducing the activation of alpha-chains of beta-integrins and their ligand ICAM-1. Survivin-induced expression of alpha-chains of beta 2-integrins is regulated by p38 MAPK and PI-3K but not by the NF-kappaB signaling pathway. Clinical relevance of our findings is supported by the in vivo association of high circulating survivin levels with an increased expression of CD11c on monocytes and granulocytes in RA patients. The results of our study demonstrate that extracellular survivin affects the phenotype of leukocytes having a possible impact on homing of inflammatory cells during arthritis.     

A model for karyotypic evolution in testicular germ cell tumors

Testicular germ cell tumor karyotypes are characterized by near-triploidy, with chromosome numbers ranging from 50 to 70, and by the frequent appearance of i(12p). The high chromosome number has been attributed to the formation of tetraploid carcinoma in situ cells followed by chromosomal losses that ultimately lead to tumor forms that are more advanced. In the present investigation, we show by analysis of the accumulated cytogenetic data on testicular germ cell tumors and computer simulations that two distinct processes are operating in the karyotypic evolution of these tumors. The results suggest that whole-chromosome changes originate from a multipolar cell division of a tetraploid cell, whereas imbalances caused by structural changes accumulate in a stepwise manner.