Safety observations frequency

The frequency of fire-induced core melt, calculated by averaging the observed frequency of the Browns Ferry type of fire over the experience of U.S. commercial nuclear power plants, was found to be lE-5 per reactor-year, or about 20% of the total core-melt probability e.slimated in the Reactor Safety Study. Kazarians and Apostolakis (1978) performed the same type of calculations under different assumptions and concluded that the frequency of core melt could be higher by a factor of 10. 

Phase II clinical trial studies are designed primarily to explore the relationship between the dose level and frequency of administration and the efficacy and safety observed in patients with a particular therapeutic indication or disorder. Normally, a primary endpoint is selected to evaluate the efficacy however, secondary endpoints are often included to establish criteria for monitoring patients in the more definitive phase III clinical trials. Phase II clinical trials are commonly... 

It is tempting to compare the mean or the median to traditionally used point-estimators for failure frequencies but that diminishes the added value of working with a distribution. Lor instance, with a point estimator, an LoC frequency of 6.68 year it would be easy to judge an observed frequency of 11.2 as a serious safety issue but in reality, it is still within possible bounds (even if it is unlikely). 

Distribution mains shall be patrolled in areas where necessary to observe factors that may affect safe operation. The patrolling shall be considered in areas of construction activity, physical deterioration of exposed piping and supports, or any natural causes that could result in damage to the pipe. The frequency of the patrolling shall be determined by the severity of the conditions that could cause failure or leakage and the subsequent hazards to public safety. 

Safety was evaluated extensively in the two phase III trials. The frequency of adverse effects observed in the 12-month controlled studies... 

Once the phase 1 has been completed, next steps include the comparison of observed human exposure data (maximum concentration, Cmax and area under the concentration-time curve, AUC) to the exposures observed in the supportive preclinical studies, prediction of the human exposure in future clinical trials (based on dose level and frequency) and the calculation of the actual safety margins provided by the repeat-dose preclinical toxicology studies. The need for safety margins (based on preclinical safety and single-dose human data) to support phase lb or phase 2 dosing is usually considered on a case-by-case basis. 

Most chemicals do not cause toxic or adverse effects until a certain dose has been given. These are called threshold chemicals. The lowest dose level at which there are no adverse effects observed in the test animals is called the No Observed Adverse Effect Level (NOAEL) and is the starting point for the calculation of the reference dose. While the terminology used may differ among regulatory agencies, the concepts are similar. In North America, the term margin of safety or exposure is used, whereas in Europe an Acceptable Operator Exposure Level (AOEL) is used. Care is taken to choose the NOAEL for an effect which is relevant to humans and that the duration, frequency and route of exposure in the test animals are relevant to the human exposure. 

Rescue and safety workers have also been studied. Nishiwaki et al. (2001) studied 27 male rescue team staff and 30 police officers, 3-45 months after the event. The study subjects showed decreased performance on the digit span test however, no effects on stabilometry and vibration perception threshold were found. Li et al. (2004) followed 27 male firefighters and 25 male police officers three years after the attack for genotoxic effects. They found an elevated frequency of sister chromatid exchanges in lymphocytes of the victims which were related to the percentage of ChE inhibition observed just after the attack. 

Vancomycin exhibits predictable pharmacokinetic properties and its clinical use has been guided by the pharmacokinetic monitoring of serum levels to determine the dose and frequency of administration. Pharmacokinetic monitoring of vancomycin, however, has become increasingly controversial given the improved safety of this antibiotic and the lack of data to support what are considered the therapeutic and toxic serum levels. Historically, the most severe toxicities of vancomycin were ototoxicity and nephrotoxicity. The incidence of nephrotoxicity has declined since its introduction possibly due to the availability of purer forms of the antibiotic. Ototoxicity has always been a rare adverse event of vancomycin, but it has been observed with excessively high concentrations of the drug in plasma [170-172]. The purpose of this section is to describe the nephrotoxicity associated with the clinical use of vancomycin. 

Topical eflornithine has a very good safety profile. The only side effects observed in the clinical trials at a higher frequency than placebo were related to skin irritation and included stinging or burning skin and rash at the site of application. 

The technique, as established, employed a Bruker AC 300 spectrometer, mainly used for solution work the MAS probe was modified for tritium observation by increasing the tuning range of the high-frequency circuitry to cover the 300-320 MHz range. Apart from the safety precautions mentioned, which were inexpensive to install, no further modifications were necessary. Typical operating conditions using the 4-mm diameter zirconia rotors (heavy walled) were as follows 320.13 MHz frequency with a 35° pulse MAS rate... 

The discovery of polymorphic N-acetylation was linked to observations on the safety, metabolism, and pharmacokinetics of the antitubercular drug, isoniazid. When urinary excretion of isoniazid was evaluated in identical twins, fraternal twins, and unrelated subjects, the variability in its excretion depended upon genetic similarity. Ultimately, in a classic experiment by Evans and colleagues that measured the plasma isoniazid concentration in subjects who had taken a single 10 mg/kg dose of isoniazid, a clear polymorphic frequency distribution was revealed with an antimode of 2.5 ug/mL. Thus, two acetylator phenotypes were identified, and the slow acetylator phenotype had a frequency of 52%, and was an autosomal recessive trait. The slow acetylator phenotype, if treated with isoniazid (INH) is at increased risk of INH-induced arthralgias, neuropathy, and hepatotoxicity. 

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