Continuation trials

In case you think that six months may not be long enough, note that similar results were shown in a year-long industry-sponsored continuation trial comparing two different antidepressants (Seroxat and imipramine) to placebo. In that study, patients who had responded to either of the antidepressants or to the placebo during the initial six-week trial were kept on their treatment for an additional year. Patients in all three groups maintained their improvement. In fact, at the end of the one-year period, those who had been treated by placebos were the... 

These continuation trials tell a very different story from that told by relapse-prevention trials. They show that there is little difference between antidepressant and placebo even when the clinical trial is extended over a longer period of time. Across the eight continuation trials that have been published, 79 per cent of patients on placebo and 93 per cent of patients on active medication remained well throughout the treatment period. In these long-term studies, placebo treatment was 95 per cent as effective as drug treatment. The authors of a meta-analysis of these trials concluded that the widely held - and probably erroneous - belief that the placebo response in depression is short-lived appears to be based largely on intuition and perhaps wishful thinking .17... 

Phase II or III long-term continuation trials, particularly those following on a short-term doubleblind efficacy trial, in order to increase subject exposure... 

Medication resistance. Sackeim et al. (1990) conducted a prospective, naturalistic study of relapse rates in 58 patients who were followed up to 1 year after ECT. The investigators used methods similar to those of Prudic et al. (1990) the patients were rated for their degree of medication resistance during the index episode before ECT. In most cases, continuation pharmacotherapy was at the discretion of the patient s private physician. Relapse following ECT was twice as common in patients who were medication resistant before ECT than in nonresistant patients (64% versus 32%). Eurther-more, among medication-resistant patients, the adequacy of continuation pharmacotherapy had no effect on relapse rates. In a lithium continuation trial post-ECT, Shapira et al. (1995) also found that patients who were medication-resistant were more likely to relapse than were patients who were not known to be medication-resistant before ECT. 

Table 9 Vector Freund Roller Compactor Parameters from Continued Trials...

Atorvastatin is an HMG Co-A reductase inhibitor. Pooled data from 21 completed and 23 continuing trials representing 3000 patient-years have shown that constipation, flatulence, dyspepsia, abdominal pain, headache, and myalgia occur in 1-3% of patients. Under 2% of atorvastatin-treated patients discontinued treatment because of an adverse event (1). Serious events in this review amounted to one patient with pancreatitis and one with cholestatic jaundice (1). There were no differences in adverse effects in 177 patients randomized for 52 weeks to either simvastatin or atorvastatin (2). 

Schlosser and Marcus [359] showed that for variations about such a continuous trial function, the induced first-order variations of Zr and Za exactly cancel, even if the orbital variations are discontinuous at a or have discontinuous normal gradients. After integration by parts, the variation of Zr about an exact solution is a surface Wronskian integral... 

In our continuing trials to extent the scope of the vinylic carbonates synthesis through the fluoroformate process, vinyl menthyl carbonate was obtained in excellent yield (80%) from menthyl fluoroformate. The polymer of vinyl menthyl carbonate was also proposed as menthol-release agent. It is noteworthy that this polymer can be easily prepared by reaction of menthyl fluoroformate with poly(vinyl alcohol) in DM50. 

Integrated drug and device Single/ Clinically continuous trialed operation Breath- activated Delivers multiple doses before reloading is needed... 

Calculate Wfjjjai from Rayleigh equation and from mass balance. Check Is = x g g If not, continue trial and error. 

Use thickness calculated from Division 2 as first trial. Continue trials until R, is close to P. 

An exothermic co-polymerization was carried out in a 12-liter batch kneader reactor. Polymer temperature, shaft torque, cooling medium inlet and outlet temperatures, and conversion wctc measured as a fimetion of batch reaction time (residence time) for several batch trials. Reaction kinetics, shaft torque relationships, and heat transfer coefficients were determined from this data and a model for a continuous reactor was developed. Continuous trials were performed using a 31-liter reactor and the results from these trials were compared against the model predictions. 

The continuous trials were performed on a twin shaft, co-rotating 31-liter kneader reactor that was equipped with a twin-screw discharge system. The rotation speed of the reactor shafts was higher than in the batch trials. Samples of the discharge from the twin-screw discharge system were tested for polymer conversion and the same process data was collected as in the batch trials. 

Based on the kinetic model, the expected conversion should have been 70%. During a continuous period of roughly 24 hours in two separate continuous trials, conversions of approximately 80% were realized in the kneader reactor (see Figure 2 a and b). This result is in close agreement to the prediction of the batch kinetic model. Improved mixing and smface renewal due to a higher shaft rotational speed in the continuous trials could be one explanation of the improved kinetics. 

To scaieup the small batch reactor torque requirements to a larger continuous reactor, 30 Nm/liter was used as the basis. Figure 2 shows the hydraulic pressure for a period of time during continuous trials 1 and 2. The average and maximum hydraulic pressures for each trial are also shown and are included in Table 1. The average hydraulic pressure of 59 bar corresponds to 26 Nm/hter, which agrees with the prediction of 30Nm/liter. 

A 12-liter twin-shaft batch kneader reactor was used to carry out an exothermic bulk polymerization. Process data was measured and polymer samples were analyzed for conversion so that models of polymerization kinetics, shaft torque, and overall heat transfer could be developed. These models were used to predict the performance of a 31-liter twin-shaft continuous kneader reactor. The kinetic and torque models accurately predicted the observed performance of the continuous reactor. Due to errors in measuring the actual polymer temperature and the low temperature differences between the polymer and coolant, the overall heat transfer coefficient observed in the continuous reactor was much higher than that predicted by the batch trials. However, the overall heat transfer coefficients for the batch and continuous trials compare well when the basis for the temperature difference was the same. 

Figure 2 (a and b) Continuous Trial Hydraulic Data and Polymer Conversion for Trials 1 and 2... 

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