scholarly journals Approval success rates of drug candidates based on target, action, modality, application, and their combinations

2021 ◽  
Author(s):  
Shingo Yamaguchi ◽  
Masayuki Kaneko ◽  
Mamoru Narukawa
Keyword(s):  
Success Rates ◽  
Drug Candidates ◽  
Target Action

scholarly journals Establishment of a Human Neuronal Network Assessment System by Using a Human Neuron/Astrocyte Co-Culture Derived from Fetal Neural Stem/Progenitor Cells

2015 ◽  
Vol 21 (1) ◽  
pp. 54-64 ◽  
Author(s):  
Kazuyuki Fukushima ◽  
Yuji Miura ◽  
Kohei Sawada ◽  
Kazuto Yamazaki ◽  
Masashi Ito
Keyword(s):  
Drug Development ◽  
Progenitor Cells ◽  
Neuronal Network ◽  
Assessment System ◽  
Assay System ◽  
Success Rates ◽  
Drug Candidates ◽  
Human Neurons ◽  
Neural Stem Progenitor Cells ◽  
Network Functions

Using human cell models mimicking the central nervous system (CNS) provides a better understanding of the human CNS, and it is a key strategy to improve success rates in CNS drug development. In the CNS, neurons function as networks in which astrocytes play important roles. Thus, an assessment system of neuronal network functions in a co-culture of human neurons and astrocytes has potential to accelerate CNS drug development. We previously demonstrated that human hippocampus-derived neural stem/progenitor cells (HIP-009 cells) were a novel tool to obtain human neurons and astrocytes in the same culture. In this study, we applied HIP-009 cells to a multielectrode array (MEA) system to detect neuronal signals as neuronal network functions. We observed spontaneous firings of HIP-009 neurons, and validated functional formation of neuronal networks pharmacologically. By using this assay system, we investigated effects of several reference compounds, including agonists and antagonists of glutamate and γ-aminobutyric acid receptors, and sodium, potassium, and calcium channels, on neuronal network functions using firing and burst numbers, and synchrony as readouts. These results indicate that the HIP-009/MEA assay system is applicable to the pharmacological assessment of drug candidates affecting synaptic functions for CNS drug development.

scholarly journals Different Therapeutic Outcomes of Benznidazole and VNI Treatments in Different Genders in Mouse Experimental Models of Trypanosoma cruzi Infection

2015 ◽  
Vol 59 (12) ◽  
pp. 7564-7570 ◽  
Author(s):  
F. H. Guedes-da-Silva ◽  
D. G. J. Batista ◽  
C. F. da Silva ◽  
M. B. Meuser ◽  
M. R. Simões-Silva ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chagas Disease ◽  
Treatment Success ◽  
Experimental Models ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Success Rates ◽  
Content Type ◽  
Drug Candidates

ABSTRACTThe lack of translation between preclinical assays and clinical trials for novel therapies for Chagas disease (CD) indicates a need for more feasible and standardized protocols and experimental models. Here, we investigated the effects of treatment with benznidazole (Bz) and with the potent experimentalT. cruziCYP51 inhibitor VNI in mouse models of Chagas disease by using different animal genders and parasite strains and employing distinct types of therapeutic schemes. Our findings confirm that female mice are less vulnerable to the infection than males, show that male models are less susceptible to treatment with both Bz and VNI, and thus suggest that male models are much more suitable for selection of the most promising antichagasic agents. Additionally, we have found that preventive protocols (compound given at 1 dpi) result in higher treatment success rates, which also should be avoided during advanced steps ofin vivotrials of novel anti-T. cruzidrug candidates. Another consideration is the relevance of immunosuppression methods in order to verify the therapeutic profile of novel compounds, besides the usefulness of molecular diagnostic tools (quantitative PCR) to ascertain compound efficacy in experimental animals. Our study aims to contribute to the development of more reliable methods and decision gates forin vivoassays of novel antiparasitic compounds in order to move them from preclinical to clinical trials for CD.

Voice Therapy With Seniors: Attendance, Outcomes, and Associated Patient Characteristics

2019 ◽  
Vol 4 (5) ◽  
pp. 814-824 ◽  
Author(s):  
Bonnie E. Smith ◽  
Ruth Huntley Bahr ◽  
Hector N. Hernandez
Keyword(s):  
Outcome Data ◽  
Voice Therapy ◽  
Similar Data ◽  
Success Rates ◽  
Reflux Symptom Index ◽  
Voice Change ◽  
Related Factors ◽  
Symptom Index ◽  
Younger Patients ◽  
Unsuccessful Treatment

Purpose The purpose of this study was to determine the attendance and success rates for seniors in voice therapy, identify any contributing patient-related factors, and compare results to existing findings for younger patients. Method This retrospective study included information from the voice records of 50 seniors seen by the same speech-language pathologist in a private practice. Analysis of attendance and outcome data divided participants into 6 groups. Outcomes for Groups 1–3 (64% of patients) were considered successful (positive voice change), while outcomes for Groups 4–6 (36% of patients) were considered unsuccessful. These data were compared to similar data collected for younger adults in a previous study. Results The attendance and success rates for seniors in this study were higher than those previously reported for younger patients. Further consideration of patient factors revealed that reports of increased stress, Reflux Symptom Index scores > 13, and higher Voice Handicap Index functional subscale scores were significant in distinguishing between patients in the successful and unsuccessful treatment outcome groups. Conclusions The relatively high attendance and success rates among this sample of seniors suggest the desire to achieve voice improvement does not diminish with age, and chances for success in voice therapy among nonfrail seniors may be greater than for younger patients.

1548: Racial Disparities in Kidney-Transplant Graft Outcomes, with a Proposal to Improve Graft Success Rates

2005 ◽  
Vol 173 (4S) ◽  
pp. 419-419
Author(s):  
Constance Marks ◽  
Carlumandarlo E.B. Zaramo ◽  
Joan M. Alster ◽  
Charles Modlin
Keyword(s):  
Racial Disparities ◽  
Kidney Transplant ◽  
Success Rates ◽  
Graft Success

Strict IVF Restrictions Could Lower Success Rates

2006 ◽  
Vol 36 (24) ◽  
pp. 40
Author(s):  
KATE JOHNSON
Keyword(s):  
Success Rates

ITI with high-dose FIX and combined immunosuppressive therapy in a patient with severe haemophilia B and inhibitor

2009 ◽  
Vol 29 (02) ◽  
pp. 155-157 ◽  
Author(s):  
H. Hauch ◽  
J. Rischewski ◽  
U. Kordes ◽  
J. Schneppenheim ◽  
R. Schneppenheim ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Immunosuppressive Agents ◽  
Tolerance Induction ◽  
Intravenous Immunoglobulins ◽  
Factor Ix ◽  
High Dose ◽  
Allergic Reactions ◽  
Success Rates ◽  
Serious Infections ◽  
History Of

SummaryInhibitor development is a rare but serious event in hemophilia B patients. Management is hampered by the frequent occurrence of allergic reactions to factor IX, low success rates of current inhibitor elimination protocols and the risk of development of nephrotic syndrome. Single cases of immune tolerance induction (ITI) including immunosuppressive agents like mycophenolat mofetil (MMF) or rituximab have been reported. We present a case of successful inhibitor elimination with a combined immune-modulating therapy and high-dose factor IX (FIX). This boy had developed a FIX inhibitor at the age of 5 years and had a history of allergic reactions to FIX and to FEIBA→. Under on-demand treatment with recombinant activated FVII the inhibitor became undetectable but the boy suffered from multiple joint and muscle bleeds. At the age of 11.5 years ITI was attempted with a combination of rituximab, MMF, dexamethasone, intravenous immunoglobulins and high-dose FIX. The inhibitor did not reappear and FIX half-life normalized. No allergic reaction, no signs of nephrotic syndrome and no serious infections were observed.

Entscheidungsprozesse beim Übersetzen: Routine und Reflexion bei Novizen und Berufsübersetzern

Fachsprache ◽  
2017 ◽  
Vol 32 (3-4) ◽  
pp. 100-121
Author(s):  
Friederike Prassl
Keyword(s):  
Decision Making ◽  
Success Rate ◽  
Knowledge Integration ◽  
Popular Science ◽  
Failure Rates ◽  
Science Text ◽  
Success Rates ◽  
Preliminary Results ◽  
Decision Making Processes ◽  
Cognitive Involvement

This article focuses on the decision-making processes involved in research and knowledge integration in translation processes. First, the relevance of decision taking intranslation is discussed. Second, the psychology of decision making as seen by Jungermann et al. (2005) is introduced, who propose a categorization of decision-making processes intofour types: “routinized”, “stereotype”, “reflected” and “constructed”. This classification is then applied to the translations by five professional translators and five novices of five segments occurring in a popular-science text. The analysis reveals that the decision-making types are distributed differently among students and professional translators, which also has to be seen against the background of whether the decisions made were successful or not. The preliminary results of this study show that students resort to reflected decisions in most cases, but with a low success rate. Professionals achieve a higher success rate when making reflected decisions. As expected, they also make more routinized decisions than students. The professionals’ success rates improve with increasing cognitive involvement, while their failure rates are relatively high when making routinized decisions, an aspect worthwhile considering in translation didactics.

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