Über den Wirkungsmechanismus des Prontosils

Ohne Zusammenfassung     

A Hierarchical Framework for Assessing Transmission Causality of Respiratory Viruses

Systematic reviews of 591 primary studies of the modes of transmission for SARS-CoV-2 show significant methodological shortcomings and heterogeneity in the design, conduct, testing, and reporting of SARS-CoV-2 transmission. While this is partly understandable at the outset of a pandemic, evidence rules of proof for assessing the transmission of this virus are needed for present and future pandemics of viral respiratory pathogens. We review the history of causality assessment related to microbial etiologies with a focus on respiratory viruses and suggest a hierarchy of evidence to integrate clinical, epidemiologic, molecular, and laboratory perspectives on transmission. The hierarchy, if applied to future studies, should narrow the uncertainty over the twin concepts of causality and transmission of human respiratory viruses. We attempt to address the translational gap between the current research evidence and the assessment of causality in the transmission of respiratory viruses with a focus on SARS-CoV-2. Experimentation, consistency, and independent replication of research alongside our proposed framework provide a chain of evidence that can reduce the uncertainty over the transmission of respiratory viruses and increase the level of confidence in specific modes of transmission, informing the measures that should be undertaken to prevent transmission.     

Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia

European Archives of Psychiatry and Clinical Neuroscience - Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the...     

The Utility of a Composite Biological Endpoint in HIV/STI Prevention Trials

A human immunodeficiency virus (HIV) as a biological endpoint in HIV prevention trials may not be feasible, so investigators have used surrogate biological outcomes. In a multisite trial, the epidemiology of STIs may be different across sites and preclude using one STI as the outcome. This study explored using a composite STI outcome to address that problem. The combined biological endpoint was the incidence of any of six new STIs (chlamydia, gonorrhea, trichomonas (women only), syphilis, herpes simplex virus type 2 infection and HIV) during a 24-month follow up period. We investigated how a composite STI outcome would perform compared to single and dual STI outcomes under various conditions. We simulated outcomes for four populations that represented a wide range of sex and age distributions, and STI prevalences. The simulations demonstrated that a combined biologic outcome was superior to single and dual STI outcomes in assessing intervention effects in 82 % of the cases. A composite biological outcome was effective in detecting intervention effects and might allow more investigations to incorporate multiple biological outcomes in the assessment of behavioral intervention trials for HIV prevention.     

A test of concordance between patient and psychiatrist valuations of multiple treatment goals for schizophrenia

Background While much discussion has been placed on the problem of poor compliance in the treatment of schizophrenia, there has been little discussion on the concordance between patients and psychiatrists, an important contributing factor to patient‐centred care. Objective To estimate the concordance between patients’ and psychiatrists’ (ordinal and cardinal) valuations of multiple goals for schizophrenia treatment and to illustrate the utility of the self‐explicated method in valuing a large number of treatment goals. Design Twenty treatment goals were identified during focus groups and literature review and were presented to patients and psychiatrists during structured interviews. Respondents were asked to rank the multiple treatment goals and rate them on a 5‐point Likert scale. Three scores were calculated based on the ranking (1–20), rating (Likert scale) (1–5) and a self‐explicated method estimated as the product of rating and ranking score (1–100). Concordance was tested using Spearman’s rho for overall ordinal rankings and via anova and F‐test for the cardinal values assigned to a specific treatment goal. Participants A total of 105 outpatients diagnosed with schizophrenia and 160 psychiatrists in Germany. Results Patient and psychiatrist values were concordant when the ordinal properties of their valuations were assessed by rating (ρ = 0.63; P = 0.002), ranking (ρ = 0.51; P = 0.02) and self‐explicated methods (ρ = 0.54; P = 0.01). Significant discordances were found when comparing the cardinal value placed on any given treatment goal using all three approaches, but the self‐explicated method produced a more discerning statistic. Relative to patients, psychiatrists significantly (P < 0.05) overvalued reduced lack of emotion, improved sexual pleasure and improved communication while undervaluing reuptake of activities of daily living, improved satisfaction and recovered capacity for work. Conclusions While there is an overall concordance between patients’ and psychiatrists’ valuation, significantly different valuations on specific goals can be identified. Here, psychiatrists tend to focus on ‘textbook’ outcomes, while patients are more concerned with functioning and living a normal life. This study also demonstrates the importance of comparing the concordance in treatment goals and the importance of preference‐based methods, such as the self‐explicated method, in the study of concordance.     

Erratum to “Applicability of in vitro tests for skin irritation and corrosion to regulatory classification schemes: Substantiating test strategies with data from routine studies” [Regul. Toxicol. Pharmacol. (2012) 402–414]

Skin corrosion or irritation refers to the production of irreversible or reversible damage to the skin following the application of a test substance, respectively. Traditionally, hazard assessments are conducted using the in vivo Draize skin test, but recently in vitro tests using reconstructed human epidermis (RhE) models have gained regulatory acceptance. In this study, skin corrosion (SCT) and irritation tests (SIT) using a RhE model were implemented to reduce the number of in vivo tests required by regulatory bodies. One hundred and thirty-four materials were tested from a wide range of substance classes included 46 agrochemical formulations. Results were assessed according to UN GHS, EU-CLP, ANVISA and US EPA classification schemes. There was high correlation between the two in vitro tests. Assessment of the SCT sensitivity was not possible due to the limited number of corrosives in the data set; SCT specificity and accuracy were 89% for all classification systems. Accuracy (63–76%) and sensitivity (53–67%) were low in the SIT. Specificity and concordance for agrochemical formulations alone in both the SCT and SIT were comparable to the values for the complete data set (SCT: 91% vs. 89% specificity, 91% vs. 89% accuracy and SIT: 64–88% vs. 70–85% specificity, 56–75% vs. 63–76% accuracy).