Short term clinical results

In the next section, we first briefly review the historical experience of highly crosslinked UHMWPE for hip replacement and summarize the general characteristics of contemporary materials in current clinical use. The next section also describes the effect of thermal treatment on the properties of fhis family of materials. In the final part of this section, we summarize the latest short-term clinical results using highly crosslinked and thermally treated UHMWPE. For more detailed information about specific highly crosslinked formulafions, see Chapter 15. 

Arredondo ]., and R.L. Worland. 1999. Bipolar shoulder arthroplasty in patients with osteoarthritis Short-term clinical results and evaluation of birotational head motion. / Shoulder Elbow Surg 8 425-429. 

Keywords— stemless hip prosthesis, physiological loading, bone remodeling, short term clinical results, young and active patients. 

Vitamin D supplements are used in diseases of bone and mineral metabolism (eg, intestinal osteodystrophy) that can present with osteomalacia. Older bisphosphonates such as etidronate have only short-term clinical value in osteoporosis or Paget s disease, since their chronic use results in osteomalacia and an increased incidence of bone fractures. The answer is (D). 

A variety of data sources are available to inform interactive programs, including prospective data sets, retrospective databases, expert opinion, and unpub-lished/published literature. Time horizon, that is, the length of time into the future considered in the analysis over which costs and outcomes are projected, is very important here [26]. For example, if a clinical trial or the published literature only report short-term results for a chronic condition, the outcomes may come into question. This is where decision-analytic models may come... 

Based on this concept of correlation between high replication rate/high persistent mutation risk, Pike et al. (1983) formulated the hypothesis of breast tissue age and developed a mathematical model to predict the effects of exposure to ovarian hormones. This model incorporates reproductive and endocrine items related to breast cancer and is able to predict the relative risk of individual situations with results that are very close to those observed in clinical trials. According to this hypothesis, both the years of exposure and the circulating serum levels of estrogens are associated to short-term breast cancer risk in postmenopausal women (Toniolo et al. 1995). 

Unlike the muscarinic receptors, repeated exposure of the neuronal receptors to nicotine, both in vivo and in vitro, results in an increase in the number of receptors similar changes are reported to occur after physostigmine is administered directly into the cerebral ventricles of rats. These changes in the density of the nicotinic receptors are accompanied by an increased release of acetylcholine. Following the chronic administration of physostigmine, however, a desensitization of the receptors occurs. Functionally nicotinic receptors appear to be involved in memory formation in clinical studies it has been shown that nicotine can reverse the effects of scopolamine on short-term working memory and both... 

In Phase 2 the studies are conducted to prove the therapeutic concept and evaluate efficacy and assure that measures of efficacy are adequate. Importantly, dose-response studies are conducted to determine the therapeutically useful dose range and to establish doses to be used in full-scale clinical trials. These studies are closely monitored and well controlled in a small to moderate numbers of patients with the condition of interest. Study results may also give some idea of common dose-related adverse events following short-term therapy. 

In projecting results of short-term trials over patients lifetimes, it is typical to present at least two of the many potential projections of lifetime treatment benefit. A one-time effect model assumes that the clinical benefit observed in the trial is the only clinical benefit received by patients. Under this model, after the trial has ended, the conditional probability of disease progression for patients is the same in both arms of the trial. Given that it is unlikely that a therapy will lose all benefits as soon as one stops measuring them, this projection method generally is pessimistic compared to the actual outcome. A continuous-benefit effect model assumes that the clinical benefit observed in the trial is continued throughout the patients lifetimes. Under this model, the conditional probability of disease progression for treatment and control patients continues at the same rate as that measured in the clinical trial. In contrast to the one-time model, this projection of treatment benefit most likely is optimistic compared to the treatment outcome. 

The only clinically available cholinergic therapy to date is an anticholinesterase (tacrine). Studies have shown short-term improvement in some aspects of memory and a delay in decline in some patients. It has been generally assumed that these effects are solely the result of enhancement of muscarinic mechanisms however, this assumption may be unwarranted. Direct muscarinic augmentation produces little measurable cognitive improvement and does not generally reproduce the memory-enhancing effects of anticholinesterases (Bruno et al. 1986 Tariot et al. 1988). 

Most efficacy trials with reboxetine have so far only been published in review articles ( 178). Most of these articles did not have peer review and do not contain the full details concerning methodology or results. This fact limits the ability to accurately determine its relative efficacy and tolerability. In short-term (4 to 8 weeks), placebo-controlled clinical trials, reboxetine produced a response (defined as at least a 50% reduction in severity scores) in 56% to 74% of patients. These results were statistically superior to placebo in most studies. Reboxetine was also found to be as effective as imipramine and desipramine in four double-blind, randomized, active-controlled (but not placebo-controlled) studies involving more than 800 outpatients or inpatients with major depression. Reboxetine produced equivalent antidepressant response rates compared with fluoxetine in two clinical trials, one of which was also placebo-controlled. However, reboxetine was reported to have improved social motivation and behavior more than fluoxetine as assessed by the newly developed Social Adaptation Self-Evaluation Scale. In all of the studies, reboxetine had a similar time (i.e., 2 to 3 weeks) to onset of the antidepressant efficacy as do other antidepressants. 

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