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BackgroundEbola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care.Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies.Methods and FindingsInclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in “cycle threshold” [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A “target value” of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis.Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%–32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%–91.1%) in Group A Ct < 20. Both mortality 95% CIs i...

These findings, in conjunction with those from other, methodologically similar studies, suggest that certain anomalies of subjective experience aggregate significantly in schizophrenia. These experiential anomalies appear to be relevant for early differential diagnosis and therefore potentially useful in the preonset detection of the schizophrenia spectrum illness.

Our research group has for several years conducted philosophically informed, phenomenological-empirical studies of morbid alterations of conscious experience (subjectivity) in schizophrenia (Sz) and its spectrum of disorders. Some of these experiential alterations constitute, in our view, the vulnerability markers to Sz – indicators that are intrinsic to this disorder and which were historically considered as constituting the phenotypic anchor of the very concept and the diagnostic validity of Sz spectrum disorders. In a more pragmatic clinical context, these indicators, considered here as symptoms, may be potentially effective for early differential diagnosis. In this study, 151 consecutive first-admitted patients (with bipolar, melancholic and organic patients excluded) diagnosed according to the ICD-10, were evaluated on a number of expressive and experiential psychopathological dimensions, with special emphasis on the experiences of perplexity, disorders of self-awareness, perceptual disorders and anomalous bodily experiences. The a priori scales derived from the item pool of a slightly modified OPCRIT and BSABS were used for analyses. Sz and schizotypal disorder scored equally on the subjective dimensions, suggesting a basic phenomenological affinity of these disorders. In contrast, anomalies of subjective experience were clearly more pronounced among the patients within, as compared to those outside the Sz spectrum.