Efficacy and safety of N-acetyl-l-leucine in Niemann–Pick disease type C

Objective: To investigate the safety and efficacy of N-acetyl-L-leucine (NALL) on symptoms, functioning, and quality of life in pediatric (≥ 6 years) and adult Niemann-Pick disease type C (NPC) patients. Methods: In this multi-national, open-label, rater-blinded Phase II study, patients were assessed during a baseline period, a 6-week treatment period (orally administered NALL 4 g/day in patients ≥ 13 years, weight-tiered doses for patients 6-12 years), and a 6-week post-treatment washout period. The primary Clinical Impression of Change in Severity (CI-CS) endpoint (based on a 7-point Likert scale) was assessed by blinded, centralized raters who compared randomized video pairs of each patient performing a pre-defined primary anchor test (8-Meter Walk Test or 9-Hole Peg Test) during each study periods. Secondary outcomes included cerebellar functional rating scales, clinical global impression, and quality of life assessments. Results: 33 subjects aged 7-64 years with a confirmed diagnosis of NPC were enrolled. 32 patients were included in the primary modified intention-to-treat analysis. NALL met the CI-CS primary endpoint (mean difference 0.86, SD = 2.52, 90% CI 0.25, 1.75, p = 0.029), as well as secondary endpoints. No treatment-related serious adverse events occurred. Conclusions: NALL demonstrated a statistically significant and clinical meaningfully improvement in symptoms, functioning, and quality of life in 6 weeks, the clinical effect of which was lost after the 6-week washout period. NALL was safe and well-tolerated, informing a favorable benefit-risk profile for the treatment of NPC. CLINICALTRIALS. Gov identifier: NCT03759639

Impfethik – Eine Skizze moralischer Herausforderungen und ethischer Kriterien

Vaccination recommendations of public health institutes and personal decisions to get vaccinated cannot be grounded on scientific evidence alone. If and under what conditions vaccinations should take place can only be decided for concrete contexts and accompanied by justification processes applying ethical norms and values.This paper offers anormative framework for vaccination ethics. It reflects the principles and argumentation of individual and social ethics and discusses public health ethical tools available in the literature. The specific challenges of autonomous and health literate behavior from ajustice perspective are examined. Also discussed is the position of the German Standing Committee on Vaccination (STIKO)

Childhood Vaccination Against Seasonal Influenza to Reduce the Overall Burden of Disease: Ethical Perspectives

Introduction Childhood immunisation against seasonal influenza promises to reduce the burden of disease through herd immunity. The option of intranasal vaccination seemed to offer a more acceptable vaccination for children, as they are perceived to be less invasive. Yet, intranasal vaccines have been recently proven not to be as effective as presumed. In Germany, contradictory recommendations of the Standing Committee on Vaccination (STIKO) first, to use and then, in October 2016, not use these vaccines have been issued for the 2016-2017 season, whereas recommendations not to use them were already issued in the USA (CDC, ACIP). This controversy spurs the discussion of immunisation programmes for children again. Despite studies discussing the effectiveness of a comprehensive immunisation programme targeting children also in the German and wider European context, an accompanying ethical discussion is missing. Methodology We discuss several policy options from different key ethical perspectives that are widely used in public health: if seasonal influenza vaccination should be intensively offered to or even made mandatory for children to decrease the societal burden of the disease. Results Various ethical perspectives reflect the question how to balance individual autonomy, personal benefit and population benefit differently. Discussion A convincing justification for suggestions on immunisation policies has to balance norms anchored in different ethical theories. There are good reasons to offer immunisation programmes against seasonal influenza to children, using a voluntary, possibly incentive-based approach

Developing child autonomy in pediatric healthcare: towards an ethical model

The changes initiated by the new National Civil and Commercial Code in Argentina underline the pediatric task to empower children's and adolescents' developing autonomy. In this paper, we have framed a model describing autonomy in child healthcare. We carried out a literature review focusing on i) the concept of autonomy referring to the absolute value of the autonomous individual, and ii) the age-driven process of competent decisionmaking development. We summarized our findings developing a conceptual model that includes the child, the pediatrician and the parents. The pediatricianchild relationship is based on different forms of guidance and cooperation, resulting in varying levels of activity and passivity. Parental authority influences the extent of autonomy, based on the level of respect of the child's moral equality. Contextual, existential, conceptual, and socialethical conditions shall be considered when applying the model to facilitate dialogue between pediatricians, children, parents and other actors