Selecting appropriate therapy

Over the next decade, seniors will spend 1.8 trillion on prescription medications. Medicare proposals to provide a drug benefit for seniors have been suggested to cost 400 billion over a 10-year period. Thus, the most elaborate of the current drug programs will pay only 22% of seniors drug costs. Enhanced use of pharmacoeconomic tenets to select appropriate therapy while considering cost and therapeutic benefits for seniors and others will become even more crucial for clinicians in the future. 

A basic grasp of normal cardiac function sets the stage for understanding the pathophysiologic processes leading to HF and selecting appropriate therapy for HF. Cardiac output is defined as the volume of blood ejected per unit of time (liters per minute) and is a major determinant of tissue perfusion. Cardiac output is the product of heart rate (HR) and stroke volume (SV) CO = HR x SV. The following describes how each parameter relates to CO. 

In addition to characterization of disease states, NMR-based metabonomic analysis offers an efficient means to monitor the response of patients to drug therapy or other therapeutic interventions. For example, in a study of patients with end-stage renal failure, the response of patients to hemodialysis was monitored. Plasma samples were obtained from healthy subjects and from patients with renal failure immediately preceding and following hemodialysis. Samples were analyzed by NMR spectroscopy and mapped with pattern-recognition methods. Samples obtained from the majority of patients following hemodialysis were observed to map more closely to the cluster of samples obtained from healthy subjects than those samples obtained prior to dialysis therapy, with the exception of one patient who responded badly to the therapy and mapped separately to all other samples [13]. Thus, this methodology can be used to select appropriate therapies for patients. 

Select appropriate insulin therapy based on onset, peak, and duration of action. 

Appropriate empiric anti-infective therapy decreases 28-day mortality compared to inappropriate empiric therapy (24% versus 39%).22 23,30 Additionally, appropriate therapy administered within 1 hour of sepsis recognition also decreases complications and mortality.22-23,30 Empiric anti-infective therapy should include one, two, or three drugs, depending on the site of infection and causative pathogens (Table 79-3). Anti-infective clinical trials in sepsis and septic shock patients are scarce and have not demonstrated differences among agents therefore, factors that determine selection are ... 

Advances in measurement of gene expression have also been phenomenal. In five years, the numbers of genes, sensitivity of the assays, and reproducibility of results have also increased significantly as has the ability to analyze the data. The measurement of gene expression has been used in several ways in cancer genetics and cancer pharmacogenomics. Gene expression has led to better ways to classify cancers and to select the appropriate therapy (Miyazato et al., 2001 Birner et al., 2001). 

Improvement of poor prognosis by selection of appropriate therapy... 

Ex vivo therapeutic strategies may take different forms. Chronic lymphocytic leukemias have been treated for long periods of time by using cell separators to reduce the burden of lymphocytosis, and to permit red cell transfusion. Laser-directed cell sorters may be used to select appropriate subpopulations of lymphocytes, which are then transfected with an appropriate gene product ex vivo and returned to the patient, where these cells will hopefully target some diseased tissue such as widespread melanoma. Expense, availability of therapy and the duration and specificity of effect currently limit the widespread application of these approaches. 

This is another area primed for active pharmacy involvement as many of these patients are in nursing homes. These patients are usually undergoing monthly medication reviews by pharmacists who can suggest appropriate dosages and combinations for the management of pain. An article by Shimp estimated that 45-80% of nursing home residents and 20-50% of elderly in the community suffer from pain. This article discusses appropriate selection of therapy and the risks for adverse effects. 

FIGURE 36-2. Recommendations for treating chronic diarrhea. Follow these steps (1) Perform a careful history and physical examination. (2) The possible causes of chronic diarrhea are many. These can be classified into intestinal infections (bacterial or protozoal), inflammatory disease (Crohn s disease or ulcerative colitis), malabsorption (lactose intolerance), secretory hormonal tumor (intestinal carcinoid tumor or VIPoma), drug (antacid), factitious (laxative abuse), or motility disturbance (diabetes mellitus, irritable bowel syndrome, or hyperthyroidism). (3) If the diagnosis is uncertain, selected appropriate diagnostic studies should be ordered. (4) Once diagnosed, treatment is planned for the underlying cause with symptomatic antidiarrheal therapy. (5) If no specific cause can be identified, symptomatic therapy is prescribed. 

The clinician should have an understanding of in vivo antimicrobial agent disposition in order to select the most appropriate therapy for a given infection and to help monitor for clinical or bacteri-ologic efficacy. Serum concentration monitoring is the most common method used to attempt to maximize efficacy and minimize toxicity of antimicrobials. Since most antimicrobials are well tolerated at their usual doses, only a select few agents (e.g., aminoglycosides, chloramphenicol, and vancomycin) are monitored routinely in the current clinical environment. There are a number of direct and indirect methods that are used to quantify the concentration of antimicrobial in an experimental sample. 

Attention must be paid to the literature on antimicrobials to assist in the selection of therapy. The results from prospective, controlled, randomized clinical trials should be evaluated whenever possible when considering appropriate antimicrobial therapy. Results from prelicensing open trials offer only limited information that may be usefnl in this regard because patients in these trials generally are not serionsly iU and are not infected with multiple resistant bacteria and other confonnd-ing factors found in most clinical situations are excluded by virtue of the study design. Therefore, comparative data in more seriously ill patients are essential for the appropriate application of new agents. ... 

Following detection of the disease, the progression is determined by the TNM system (tumour, nodes, metastases) and the most appropriate therapy for the individual concerned is selected. 

Surgery is the normal method for local control of the breast cancer and, if used at an early stage, produces a cure in many patients. Treatment may involve removal of the primary tumour, radical mastectomy with radiation, or tylectomy. However, after surgery, more than half the patients will relapse, with a mean duration of survival of about 3 years [38]. The selection of appropriate follow-up treatment for the patient who develops recurrence or metastases will have a considerable influence on the patient s duration of survival. A treatment scheme for patients with metastatic breast cancer has been summarized by Allegra [39] and a summary of factors influencing selection of therapy by Clarysse [40]. 

The goal of the symposium, which is presented in this book, was to demonstrate the anatomical and biomechanical fundamental principles which are significant for the selection of the appropriate therapy. 

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