The use of the bootstrap statistical method for the pharmacoeconomic cost analysis of skewed data.

In pharmacoeconomics, the comparison of the costs of 2 different drugs used for the same treatment is of great interest. The problem is especially challenging when the drugs are likely to produce costly adverse effects in a small number of patients, which is often the case. The data are then skewed and traditional statistical methods to analyse the difference in the mean costs produced by 2 treatments may be inappropriate. The bootstrap method is presented as an alternative approach. A pharmacoeconomic cost-analysis example is presented and used throughout this article.

Plasma amino acid and serum unesterified fatty acid deficits and the effect of nutritional support in chemotherapy treatment.

The deficits in plasma amino acids and serum unesterified fatty acids of cancer patients undergoing chemotherapy and/or radiation therapy were studied to delineate the special requirements of the patients and efficacy of our nutritional therapy. Seven general surgery patients and 13 patients treated by the Head-Neck Service had baseline levels measured as part of their nutritional evaluation prior to surgical treatment of their cancers. Fifteen chemotherapy outpatients maintained on their regular diets had fasting levels analyzed. Twenty-six patients who were admitted for their therapy had their intake of the regular hospital diet supplemented with a low-residue enteral diet formula (Vivonex High Nitrogen Diet); parenteral nutrition was used only if their oral intake was totally inadequate. Baseline and sequential measurements were made of plasma amino acid and serum unesterified fatty acid levels by gas liquid chromatographic techniques. Before operation the patients had normal levels of amino acids except for a significant deficiency of threonine and glycine observed in patients with head-neck tumors. Outpatients with and without hepatic metastases had significantly depressed levels of the essential amino acids valine, leucine, threonine, and methionine and the nonessential amino acids serine, glycine, and proline. The baseline levels of the patients admitted for treatment had similar deficiencies except for more evidence of lysine deficiency. Patients supported with total parenteral nutrition had rapid elevation of the amino acid levels. The patients whose intake was supplemented with the oral diets had improvement in their amino acid levels, but the deficiency in the leucine and threonine fractions persisted up to 4 weeks of therapy. Although the lysine levels were normal when first analyzed, significant differences developed in the patients without hepatic metastases after the start of chemotherapy with return to normal only after chemotherapy was discontinued. Fatty acid levels were not significantly different between the cancer groups except for preoperative elevated oleic acid levels noted in the general surgery tumor group; there were no deficiencies in the essential fatty acids. These studies indicate a need for enteral formulas with adequate branched-chain amino acids and enrichment with threonine and lysine for supplementing the nutrition of the cancer patient who is undergoing chemotherapy.

The outcome of surgical treatment as related to the response of the serum albumin level to nutritional support.

Selected nutritional parameters were studied in critically ill surgical patients maintained by parenteral-enteral nutritional support to delineate the nutritional deficits and relate the course of these patients to the nutritional status. Twenty-one of 34 patients had albumin levels of less than 3.5 grams per cent upon admission, and the albumin levels decreased even further after admission. The patients with traumatic injuries had the greatest loss in body weight and urinary nitrogen excretion. Although such large numbers of these patients had depressed serum albumin levels, the survivors were able to increase the serum albumin level to 3.5 grams per cent with intense nutritional support, whereas those not surviving such support were not able to increase the serum albumin level. The response of the serum albumin level to nutritional support is a good indicator as to the same factors preventing survival and effective use of the nutritional elements.

Nutritional deficiencies and nutritional support therapy in geriatric cancer patients.

Nutritional deficits and their correction were studied in 45 cancer patients (age range, 60--86 years) who were undergoing various modalities of cancer therapy. Their nutritional status was maintained with a variety of commercially available special diets, and serum albumin concentrations were sequentially determined in order to gauge the efficacy of the nutritional support. Serum albumin levels were preserved when nutritional support was employed in surgical therapy. However, patients undergoing palliative chemotherapy or radiotherapy responded only to adequate levels of the standard hospital diet with or without supplements of special enteral diets. In the survivors, albumin levels were maintained; in the nonsurvivors, albumin levels decreased. This group of older patients tolerated nutritional support therapy, especially when it was carefully monitored. Satisfactory nutritional therapy can be achieved by use of appropriate enteral formulas. The method lends itself to adequate management in the outpatient or nursing-home situation during certain phases of cancer.

The absence of protein--sparing effects utilizing crystalline amino acids in stressed patients.

The protein-sparing effects of the peripheral infusion of crystalline amino acids (PAA) was studied metabolically in selected surgical patients subjected to various degrees of stress. Twenty-one patients (sixteen cancer patients receiving chemotherapy and/or radiotherapy, three with major abdominal traumatic injuries and four with paralytic ileus) were infused with 2 1/24 hours of a solution of 4.2% Travasol amino acids with only 5% glucose as a source of nonprotein calories. One-half of the cancer patients were also allowed ad libitum oral intake of a regular hospital diet or Vivonex-HN. The nutritional status was evaluated by measuring changes in body weight, serum albumin levels and nitrogen balance. Body weight decreased in only the trauma patients. When these solutions were the sole source of nutrients all patients were in negative nitrogen balance and had significant decreases in their serum albumin levels. Serum albumin levels were preserved only when extra sources of calories were provided. The infusion of the crystalline amino acids without adequate levels of nonprotein energy did not conserve protein in these stressed patients.

The leukocyte adherence-inhibition assay as a diagnostic test for multiple sclerosis: study of a substance found in MS blood.

We have modified and adapted two well-accepted cancer immunology research techniques to study blood leukocyte phenomena of MS patients. The LAI test of Halliday and Miller and the 3 molar potassium chloride (3M KCl) tumor antigen extraction technique of Dean and McCoy were adapted to extract from pooled MS whole blood an MSRM. The LAI test results of 53 of 58 MS patients (91%) were considered positive, but only three of 75 control subjects (4%) were positive when tested against the MSRM. This indicates that patients with MS had a greater specific reactivity to the MSRM than did the control subjects (healthy individuals and patients with disease other than MS). The specificity and reproducibility of this reaction were tested with materials prepared from various malignant diseases. Sensitized leukocytes showed consistently higher reactivity to antigen extracts prepared from corresponding types of tumors than to extracts prepared from tumors of other histological types. Our results indicate that (1) the LAI test is able to corroborate the neurological diagnosis of MS and (2) there is a blood constituent found only in the MS patient.