Safety concomitant

Moisture. The effect of moisture on expls, propints and pyrots can be deleterious in terms of reliability, efficiency and safety. This unwanted ingrenlent can add uncertainty and possible hazard in the manuf, storage and eventual use of ammo. Moisture adds to the costs of ammo in many ways. These include less effective material being available per unit volume, with concomitant increases in malfunction rate, curtailed shelf life because of structural failures occasioned by moisture-generated chem reaction products and the cost of many investigations undertaken to understand and prevent effects (Expls Refs 6,8, 11, 12, 15,17,21,26, 28,31,34,35,39, 40,. 41, 43, 44, 46, 48, 52 54 Propints Refs 9, 13, 16, 19, 21, 23, 27, 29, 37 53 Pyrots Refs 5, 7,10, 14,18, 20, 23, 24, 28, 30 38)... 

These qualities make cromolyn an option for patients with multiple comorbidities and concomitant medications. Cromolyn is an alternative for patients in whom antihistamines are too sedating and impair work and school performance. Additionally, cromolyn helps to prevent AR when taken prior to exposure, such as visiting a home with a pet.18 Due to its excellent safety profile, cromolyn is a first-line agent in children with AR.11,12... 

With a common intermediate from the Medicinal Chemistry synthesis now in hand in enantiomerically upgraded form, optimization of the conversion to the amine was addressed, with particular emphasis on safety evaluation of the azide displacement step (Scheme 9.7). Hence, alcohol 6 was reacted with methanesul-fonyl chloride in the presence of triethylamine to afford a 95% yield of the desired mesylate as an oil. Displacement of the mesylate using sodium azide in DMF afforded azide 7 in around 85% assay yield. However, a major by-product of the reaction was found to be alkene 17, formed from an elimination pathway with concomitant formation of the hazardous hydrazoic acid. To evaluate this potential safety hazard for process scale-up, online FTIR was used to monitor the presence of hydrazoic acid in the head-space, confirming that this was indeed formed during the reaction [7]. It was also observed that the amount of hydrazoic acid in the headspace could be completely suppressed by the addition of an organic base such as diisopropylethylamine to the reaction, with the use of inorganic bases such as... 

Concomitant or prior medications may be used in either safety or efficacy analyses. The presence of specific medications may be used as covariates for inferential analyses. Also, medications are often summarized to show that the therapies under study come from medically comparable populations. Medications may be used to determine protocol compliance and to help define a protocol-compliant study population. Concomitant medications may be examined to determine whether they interact with study therapy or whether they can explain the presence of certain adverse events. From a CDISC perspective, prior medications would be considered a finding while concomitant medications would be considered an intervention. 

Test, control, and reference substances used in worker safety and reentry testing also must be verified for their shelf-life stability prior to (or concomitantly with) use in a particular study. This means assuring stability... 

The efficacy document E7 (ICH 1993) states that the drug should be studied in all patient groups, elderly included, for which they have a significant utility. It also includes new uses, new formulations and new combinations of established medicinal products when there is specific reason to expect that conditions common in the elderly (e.g. renal or hepatic impairment, impaired cardiac function, concomitant illness or medication) are likely to be encountered. This also applies for when the geriatric patients response (safety, tolerability, efficacy) is different from the nongeriatrics. ... 

While steady improvements in the efficiency of delivery of medical care and prescribing safety will create concomitant improvements in clinical research over time, it is likely that the pace of such advances will not satisfy the demands of sponsors for faster, higher quality and less expensive trials. 

Some articles, for example, include an identical table of effective and lethal doses of high potency Fentanyl derivatives. The estimated safety margins are as high as 30,000. I could find no source for these data. I sent out several inquiries but thus far have received no definitive answers. I also discussed the questions with Harry Salem, who continues to study the toxicology of opioids at Edgewood. He is hopeful that the concomitant use of drugs tailored to suppress the effect of potent opioids on respiration may produce much safer agents. 

Safety and efficacy have not been established as initial monotherapy, for conversion to monotherapy from AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate or for simultaneous conversion to monotherapy from 2 or more concomitant AEDs. 

Phase 3a Confirmation of efficacy and safety (benefit/risk) Comparison with standard therapy and/or placebo Long-term safety Patients with the targeted disease, including (as much as possible) those with complications and/or concomitant conditions... 

Specificity to the human target confers a very desirable safety advantage for prospective patients, in terms of lack of unpredictable side effects, but concomitantly it often presents a challenge to the developer, owing to lack of adequate cross-reactivity with the... 

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