SPECIAL REQUIREMENTS FOR TOXICITY TESTING OF ORAL COMPOUNDS ADMINISTERED CONTINUOUSLY OR CYCLICALLY

1974 ◽  
Vol 77 (1_Suppla) ◽  
pp. S387-S408 ◽  
Author(s):  
G. A. Overbeek ◽  
H. W. Hornstra ◽  
E. B. van Julsingha ◽  
J. P. Mumford ◽  
I. Zayed
Keyword(s):  
Side Effects ◽  
Oral Contraceptives ◽  
Predictive Value ◽  
Animal Studies ◽  
Toxicity Testing ◽  
Prolonged Treatment ◽  
Safety Studies ◽  
Short And Long Term ◽  
Dose Levels

ABSTRACT The authors feel that several reasons exist for considering contraceptives as a special class of drugs, which therefore require special safety studies. Apart from the usual short and long term studies, particular attention should be paid to the reversibility of the induced infertility, and to its possible consequences for subsequent offspring. A possible risk of damage to the foetus is partially outweighed by the low risk of pregnancy during the treatment periods with oral contraceptives. The procedures used in the Organon laboratories are briefly described. Principles on which we base the choice of dose levels and the duration of the various studies are discussed. The paucity of available data from toxicity studies in animals has prevented the presentation of a summary allowing an appraisal of the predictive value of the current methods in toxicology. Nevertheless, a few examples are given which demonstrate the need for more predictive methods. The present lack of knowledge on side effects in humans after prolonged treatment with oral contraceptives has created a feeling of uneasiness. This in its turn has resulted in some excessive regulatory requirements for very long term animal studies. In our opinion, the predictive value of these studies is extremely low because of the inadequacy of the available animal models. More value can be attached to the monitoring of side effects in humans and efforts in this direction should be increased. The Organon system of monitoring the side effects of its marketed preparations is briefly described. It is not considered feasible to standardize regulatory toxicity requirements for the time being, which should not prevent us from aiming at reasonable, more generally accepted methods of study.

scholarly journals Influences on Attitudes Regarding Potential COVID-19 Vaccination in the United States

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 582 ◽  
Author(s):  
Kendall Pogue ◽  
Jamie L. Jensen ◽  
Carter K. Stancil ◽  
Daniel G. Ferguson ◽  
Savannah J. Hughes ◽  
...  
Keyword(s):  
United States ◽  
Structural Equation Modeling ◽  
Side Effects ◽  
Structural Equation ◽  
The United States ◽  
Equation Modeling ◽  
Vaccine Acceptance ◽  
The World ◽  
Short And Long Term

The COVID-19 pandemic continues to ravage the world, with the United States being highly affected. A vaccine provides the best hope for a permanent solution to controlling the pandemic. However, to be effective, a vaccine must be accepted and used by a large majority of the population. The aim of this study was to understand the attitudes towards and obstacles facing vaccination with a potential COVID-19 vaccine. To measure these attitudes a survey was administered to 316 respondents across the United States by a survey corporation. Structural equation modeling was used to analyze the relationships of several factors with attitudes toward potential COVID-19 vaccination. Prior vaccine usage and attitudes predicted attitudes towards COVID-19 vaccination. Assessment of the severity of COVID-19 for the United States was also predictive. Approximately 68% of all respondents were supportive of being vaccinated for COVID-19, but side effects, efficacy and length of testing remained concerns. Longer testing, increased efficacy and development in the United States were significantly associated with increased vaccine acceptance. Messages promoting COVID-19 vaccination should seek to alleviate the concerns of those who are already vaccine-hesitant. Messaging directed at the benefits of vaccination for the United States as a country would address the second predictive factor. Enough time should be taken to allay concerns about both short- and long-term side effects before a vaccine is released.

scholarly journals Influences on Attitudes regarding Potential COVID-19 Vaccination in the United States

2020 ◽  
Author(s):  
Kendall Pogue ◽  
Jamie Jensen ◽  
Carter Stancil ◽  
Daniel Ferguson ◽  
Savannah Hughes ◽  
...  
Keyword(s):  
United States ◽  
Side Effects ◽  
Predictive Factor ◽  
Structural Equation ◽  
The United States ◽  
Vaccine Acceptance ◽  
Equation Modelling ◽  
The World ◽  
Short And Long Term

The COVID-19 pandemic continues to ravage the world, with the United States being highly affected. A vaccine provides the best hope for a permanent solution to controlling the pandemic. However, to be effective, a vaccine must be accepted and used by a large majority of the population. Structural equation modelling was used to analyze the relationships of several factors with attitudes toward potential COVID-19 vaccination. The survey was administered to 316 respondents across the United States by a survey corporation. Prior vaccine usage and attitudes predicted attitudes towards COVID-19 vaccination. Assessment of the severity of COVID-19 for the United States was also predictive. Approximately 68% of all respondents were supportive of being vaccinated for COVID-19, but side effects, efficacy, and length of testing remained concerns. Longer testing, increased efficacy and development in the United States were significantly associated with increased vaccine acceptance. Messages promoting COVID-19 vaccination should seek to alleviate the concerns of those who are already vaccine-hesitant. Messaging directed at the benefits of vaccination for the United States as a country would address the second predictive factor. Enough time should be taken to allay concerns about both short and long-term side effects before a vaccine is released.

scholarly journals Predictors of time to remission and treatment failure in patients with Graves’ disease treated with propylthiouracil

2009 ◽  
Vol 32 (3) ◽  
pp. 199 ◽  
Author(s):  
Hakan Cinemre ◽  
Cemil Bilir ◽  
Feyzi Gokosmanoglu ◽  
Nermin Akdemir ◽  
Besir Erdogmus ◽  
...  
Keyword(s):  
Side Effects ◽  
Treatment Failure ◽  
Flow Rate ◽  
Free Thyroxine ◽  
Prolonged Treatment ◽  
Superior Thyroid Artery ◽  
Graves Disease ◽  
Long Term Treatment ◽  
Artery Flow

Purpose: Propylthiouracil is one of the thionamides used in the treatment of Graves’ disease. The drug has serious side effects and long-term treatment might be needed to achieve remission. We designed this study to evaluate the clinical and thyroid Doppler characteristics that might predict time to remission and treatment failure in propylthiouracil treated Graves’ patients. Methods: 26 patients, among 134 presenting to our university hospital outpatient clinic between Feb -July 2007 and with first time diagnosis of clinical thyroid dysfunction, were clinically and ultasonographically diagnosed with Graves’ disease. Doppler parameters, serum thyrotropin, free thyroxine and free triiodothyronine were measured at the beginning of the study and thyroid studies were repeated every 4 weeks until remission. Propylthiouracil 300 mg/day was started for each patient at the time of diagnosis and doses were titrated according to repeat thyroid studies. Patients were treated and followed up for 18 months. Results: Treatment failure was associated with smoking (P = 0.001) and male gender (P= 0.037). Stepwise multiple regression analysis revealed that age, free thyroxine and superior thyroid artery flow rate were predictors of time to remission (P= 0.001, 0.002 and 0.003, respectively). Conclusion: The time to remission in Graves patients treated with propylthiouracil can be predicted using age, serum free thyroxine and superior thyroid artery flow rate. This may help early consideration of alternative treatment for the patients requiring prolonged treatment for remission or for those who fail medical treatment. This would decrease unnecessary, long-term propylthiouracil exposure with its serious side effects.

scholarly journals Predictive Value of the ABCD3-I for Short- and Long-Term Stroke after TIA with or without sICAS

2021 ◽  
Author(s):  
Xuewei Xie ◽  
Jing Jing ◽  
Xia Meng ◽  
Zixiao Li ◽  
Pan Chen ◽  
...  
Keyword(s):  
Predictive Value ◽  
Short And Long Term

scholarly journals Expression of MICA in Zero Hour Biopsies Predicts Graft Survival After Liver Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Thomas Resch ◽  
Hubert Hackl ◽  
Hannah Esser ◽  
Julia Günther ◽  
Hubert Schwelberger ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Function ◽  
Graft Survival ◽  
Predictive Value ◽  
Risk Index ◽  
Graft Function ◽  
Inverse Correlation ◽  
Rank Test ◽  
Short And Long Term

In search for novel biomarkers to assess graft quality, we investigated whether defined candidate genes are predictive for outcome after liver transplantation (LT).Zero-hour liver biopsies were obtained from 88 livers. Gene expression of selected candidate markers was analyzed and correlated with clinical parameters as well as short and long-term outcomes post LT. Whereas both, the calculated Eurotransplant Donor-Risk-Index and the donor body mass index, had either a poor or no predictive value concerning serum levels indicative for liver function (ALT, AST, GGT, bilirubin) after 6 months, chronological donor age was weakly predictive for serum bilirubin (AUC=0.67). In contrast, the major histcompatibility complex class I related chain A (MICA) mRNA expression demonstrated a high predictive value for serum liver function parameters revealing an inverse correlation (e.g. for ALT: 3 months p=0.0332; 6 months p=0.007, 12 months 0.0256, 24 months p=0.0098, 36 months, p=0.0153) and proved significant also in a multivariate regression model. Importantly, high expression of MICA mRNA revealed to be associated with prolonged graft survival (p=0.024; log rank test) after 10 years of observation, whereas low expression was associated with the occurrence of death in patients with transplant related mortality (p=0.031). Given the observed correlation with short and long-term graft function, we suggest MICA as a biomarker for pre-transplant graft evaluation.

scholarly journals “How Long Have I Got?” in Stage IV NSCLC Patients With at Least 3 Months Up to 10 Years Survival, Accuracy of Long-, Intermediate-, and Short-Term Survival Prediction Is Not Good Enough to Answer This Question

2021 ◽  
Vol 11 ◽  
Author(s):  
Huiru Guo ◽  
Hegen Li ◽  
Lihua Zhu ◽  
Jiali Feng ◽  
Xiange Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Predictive Value ◽  
Stage Iv ◽  
Short Term ◽  
Term Survival ◽  
Alive With Disease ◽  
Short And Long Term ◽  
Nsclc Patients ◽  
Long Term Survivors

BackgroundMost lung cancer patients worldwide [stage IV nonsmall cell lung cancer (NSCLC)] have a poor survival: 25%–30% die <3 months. Yet, of those surviving >3 months, 10%–15% (70,000–105,000 new patients worldwide per year) survive (very) long. Surprisingly, little scientific attention has been paid to the question, which factors cause the good prognosis in these NSCLC stage IV long survivors. Therefore, “How long do I still have?” currently cannot be accurately answered. We evaluated in a large group of 737 stage IV NSCLC patients surviving 3.2–120.0 months, the accuracies of short- and long-term survival predictive values of baseline factors, radiotherapy (RT), platinum-based chemotherapy (PBT), and tyrosine kinase inhibitor targeted therapy (TKI-TT).MethodsThis is a noninterventional study of 998 consecutive first-onset stage IV NSCLC patients. A total of 737 (74%) survived 3.2–120.0 months, 47 refused RT, PBT, and TKI-TT. Single and multivariate survival analysis and receiver operating curve (ROC) analysis were used with dead of disease (DOD) or alive with disease (AWD) as endpoints.ResultsThe median survival (16.1 months) of 47 patients who refused PBT, RT, and TKI-TT was significantly worse than those with RT, PBT, and/or TKI-TT (23.3 months, HR = 1.60, 95% CI = 1.06–2.42, p = 0.04). Of these latter 690 patients, 42% were females, 58% males, median age 63 years (range 27–85), 1-, 2-, 5-, and 10-year survival rates were 74%, 49%, 16%, and 5%. In total, 16% were alive with disease (AWD) at the last follow-up. Pathology subtype (adenocarcinoma vs. all others), performance score, TNM substage, the number of PBT cycles and TKI-TT had independent predictive value. However, with the multivariate combination of these features, identification results of short-term nonsurvivors and long-term survivors were poor.ConclusionsIn stage IV NSCLC patients with >3 months survival, baseline features, and systemic therapeutic modalities have strong survival predictive value but do not accurately identify short- and long-term survivors. The predictive value of other features and interventions discussed should be investigated in the worldwide very large group of stage IV NSCLC patients with >3 months survival.

Single Donor Plasma in Therapeutic Plasma Exchange for Myasthenia Gravis

1987 ◽  
Vol 10 (5) ◽  
pp. 315-318 ◽  
Author(s):  
R. Mantegazza ◽  
E. Bruzzone ◽  
B. Regi ◽  
D. Peluchetti ◽  
M. Marconi ◽  
...  
Keyword(s):  
Side Effects ◽  
Myasthenia Gravis ◽  
Plasma Exchange ◽  
Optimal Schedule ◽  
Therapeutic Plasma Exchange ◽  
Single Donor ◽  
Short And Long Term ◽  
Donor Plasma

Thirty-seven myasthenic patients were treated with therapeutic plasma exchange (TPE) on different performance schedules using either random or single donor plasma. The two schedules had the same effects in terms of efficacy but single donor replacement gave significantly less side effects in the short and long term. A two exchange procedure on alternate days associated with immunosuppression seems to be an optimal schedule for the treatment of myasthenic patients. A single donor two-exchange on alternate days procedure appears to be safe, useful and can be repeated in patients who need frequent TPE.

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