Quality of life measurement clarifies the cost-effectiveness of Helicobacter pylori eradication in peptic ulcer disease and uninvestigated dyspepsia.

OBJECTIVES: Previous economic studies of Helicobacter pylori eradication in dyspepsia and peptic ulcer disease have not measured quality of life using utilities (preference probabilities), which are needed to compare the cost-effectiveness of such treatment to other health care interventions. The goals of this study were to measure quality of life in patients with dyspepsia or peptic ulcer and apply these measurements to published models of disease management to determine cost-effectiveness in dollars per quality-adjusted life year (QALY) gained. METHODS: Utilities for dyspepsia and peptic ulcer disease were measured in adult patients (n = 73) on chronic acid suppression for peptic ulcer or ulcer-like dyspepsia. Median utility values were applied to the results of published cost-effectiveness analyses and a previously validated dyspepsia model. Cost-utility ratios for early H. pylori eradication in uninvestigated dyspepsia and peptic ulcer disease were then computed. RESULTS: The total disutility, or lost quality of life, for an ulcer was 0.11 QALY, of which 0.09 QALY was attributed to dyspeptic symptoms. After these results were incorporated into published studies, cost-utility ratios for ulcer treatment varied from $3,100 to $12,500 per QALY gained, whereas estimates for uninvestigated dyspepsia management ranged from $26,800 to $59,400 per QALY. Sensitivity analyses indicated a range of $1,300 to $27,300 per QALY for management of duodenal ulcer and $15,000 to $129,700 per QALY for dyspepsia. CONCLUSIONS: Strategies that emphasize early H. pylori eradication were cost-effective for patients with peptic ulcer and possibly cost-effective for patients with uninvestigated dyspepsia, relative to other medical interventions. Dyspeptic symptoms cause significant disutility that should be incorporated in future cost-effectiveness analyses of treatment strategies.

Review article: faecal occult blood testing for colorectal cancer.

Major health organizations recommend colorectal cancer screening using faecal occult blood tests, sigmoidoscopy or both for patients 50 years of age or older who are at average risk for colorectal cancer. However, no specific recommendations have been made regarding choice of test from among the tests currently or soon to be available. Therefore, to aid clinicians in rationally choosing a particular test for faecal occult blood, published data are reviewed regarding the performance characteristics, strengths and weaknesses of the various faecal occult blood tests. New studies suggest that immunochemical tests (e.g. HemeSelect) or a combination of sensitive guaiac tests and immunochemical tests (e.g. Hemoccult Sensa and HemeSelect) are the most sensitive, specific tests for detecting colorectal carcinoma and colorectal polyps > or =1 cm.

A comparison of fecal occult-blood tests for colorectal-cancer screening.

BACKGROUND: Hemoccult II, a widely used guaiac test for fecal occult blood, has a low sensitivity for detecting colorectal neoplasms in asymptomatic patients at average risk. In such patients, the performance characteristics of screening tests developed to improve on Hemoccult II are not known. METHODS: A set of three fecal occult-blood tests--Hemoccult II; Hemoccult II Sensa, a more sensitive guaiac test; and HemeSelect, an immunochemical test for human hemoglobin--was mailed to all patients 50 years of age or older who were scheduled for personal health appraisals at the Kaiser Permanente Medical Center in Oakland, California. The performance of each test and of a combination test (HemeSelect to confirm positive Hemoccult II Sensa results) was evaluated by identifying screened patients who had colorectal neoplasma (carcinoma or a polyp > or = 1 cm in diameter) in the two years after screening. RESULTS: Of the 10,702 eligible patients, 8104 (75.7 percent) had at least one interpretable sample and were screened on the basis of at least one test; 96 percent of these patients had complete two-year follow-up. The sensitivity of the tests for detecting carcinoma was lowest with Hemoccult II (37.1 percent; 95 percent confidence interval, 19.7 to 54.6 percent), intermediate with the combination test (65.6 percent; 95 percent confidence interval, 47.6 to 83.6 percent) and with HemeSelect (68.8 percent; 95 percent confidence interval, 51.1 to 86.4 percent), and highest with Hemoccult II Sensa (79.4 percent; 95 percent confidence interval, 64.3 to 94.5 percent). The specificity for detecting carcinoma was 86.7 percent with Hemoccult II Sensa, 94.4 percent with HemeSelect, 97.3 percent with the combination test, and 97.7 percent with Hemoccult II. HemeSelect and the combination test detected more colorectal carcinomas and polyps than Hemoccult II, with only slight increases in the number of colonoscopies needed. CONCLUSIONS: HemeSelect and a combination test in which HemeSelect is used to confirm positive Hemoccult II Sensa results improve on Hemoccult II in screening patients for colorectal carcinoma.

Hemoccult screening in detecting colorectal neoplasm: sensitivity, specificity, and predictive value. Long-term follow-up in a large group practice setting.

STUDY OBJECTIVE: To determine the sensitivity, specificity, and predictive value of Hemoccult II tests for detecting colorectal neoplasm (colorectal carcinoma or polyp or both). STUDY DESIGN: Prospective analyses of asymptomatic patients (greater than or equal to 45 years) followed for 4 years after screening with Hemoccult II testing and retrospective analyses of patients, with known colorectal carcinoma or polyps or both who had Hemoccult II testing within 2 years of diagnosis. SETTING: A large, health maintenance organization practice. MEASUREMENTS AND MAIN RESULTS: In the prospective analysis, the sensitivity of Hemoccult II was 50% for colorectal carcinoma diagnosed within 1 year of testing, 43% within 2 years, and 25% within 4 years. For polyps, sensitivity was 36% at 1 year, 28% at 2 years, and 17% at 4 years. Specificity was 99%. The predictive value of a positive test for colorectal carcinoma was 8% at 1 year, 10% at 2 years, and 11% at 4 years. On the basis of the retrospective analyses, the sensitivity of Hemoccult II for colorectal carcinoma diagnosed within 1 year of testing was 66% and was 61% within 2 years. Many of these patients had symptoms when tested. CONCLUSIONS: An asymptomatic patient age 45 or older with a positive Hemoccult II test has about a chance of 1 in 10 for having colorectal carcinoma and a 1-in-3 chance of having either a colorectal carcinoma or polyp: The same patient with a negative Hemoccult test has a 0.2% chance of having a colorectal carcinoma diagnosed within 2 years of testing and a 0.7% chance of having a polyp. Within 4 years of testing the chance increases to 0.5% for colorectal carcinoma and 1.5% for polyps. If Hemoccult II slides are the only screening method used for detecting asymptomatic colorectal neoplasms, 50% to 60% of lesions will remain undetected. Clinical interpretation of Hemoccult screening requires appreciation of its limits as well as its benefits.

Cost benefits of hemoccult screening for colorectal carcinoma.

Hemoccult screening for colorectal carcinoma was begun in 1979 at the Kaiser Permanente Medical Center, Oakland, California, as part of a program for periodic health examinations. A concomitant cost-benefit analysis was conducted to determine the long-term medical care costs and survival benefits of this procedure. Of 14,041 patients greater than or equal to 45 years of age mailed hemoccult slides, 10,255 (70.3%) returned them at the time of their examination. One hundred twelve (1.1%) were positive, and 12 colorectal carcinomas were detected. Additionally, 13 patients with one or more polyps greater than or equal to 1 cm and 45 patients with other gastrointestinal sources of blood were found. Of the screened cases of colorectal carcinoma, 50% were in Dukes' stage A compared with 25% found in this stage in our institution in 1974, when screening was not done. Five-year Dukes' stage-specific medical care costs and mortality rates were developed from the 1974 cases and were then applied to the screened cases of colorectal cancer. A savings in medical care costs of +14,685 and a projected increase of 22 years in life expectancy was found.

Structural and functional abnormality of ectopic testes in rats.

Some males of a mutant strain of King-Holtzman rats exhibit an anomalous heritable defect manifested as either unilateral or bilateral ectopic testes. In the adult, these testes contain seemingly immature Sertoli and Leydig cells, seminiferous tubules greatly reduced in diameter, and exhibit arrested spermatogenesis. Thus, the affected testis is essentially sterile. An inability to produce normal amounts of testosterone and androstenedione by these gonads is probably a reflection of changes that have been effected in their Leydig cells. Thus, this study suggests that abnormal function of the Leydig and Sertoli cells and seminiferous tubule failure in these mutant animals result from the physiologically cryptorchid condition.

Ectopic testes in the Norway rat.

Animals with ectopic testes, some unilateral (on either the right or left side) and some bilateral, have appeared in a colony of King-Holtzman rats. This heritable defect has been given the genetic symbol "ect." Females carrying the gene are unaffected by it. When such females are bred to apparently normal males, they produce no ect offspring. Since 25% of their F2 generation carry the gene, it is assumed it is autosomal recessive. Studies involving selective breeding for males with ectopic testes indicate that some males have genomes resistant to the expression of the ect gene and that the apparent thresholds essential to left side, right side, and bilateral expression appear to be a secondary control of the multifactorial type.

Ectopic testes: a heritable mutation in the King-Holtzman rat: androgen-binding protein in testes and epididymides.

Assays of androgen-binding protein (ABP) were carried out on testes, and epididymal heads and tails. This strain of rat exhibits a heritable mutation physically manifested as unilateral or bilateral maldescended (ectopic) testes. When present, they are found immediately cranial to the external inguinal ring in the superficial connective tissue on the ventral body wall. Charcoal-extracted cytosols were preincubated with 16 nM tritiated 5 alpha-dihydrotestosterone ( [3H] DHT) for 16-20 h at 4 degrees C and ABP was separated by polyacrylamide gel electrophoresis under steady-state conditions in the presence of 2 nM [3H] DHT. The gels were transversely cut into 2.1-mm thick slices and serially counted in a liquid scintillation counter. Binding of [3H] DHT to ABP was assumed to be 1:1 and the sum dpm of the ABP-containing slices corrected for background was expressed as pmol DHT bound/mg protein. Compared to normal male siblings, cytosol ABP levels on the ectopic side in unilateral ectopic rats were 78% and 93% lower than normal in epididymal heads and tails, respectively; whereas similar values for either side in bilateral ectopic rats were 88% and 99%. The above differences indicated in the cytosol ABP levels were significant at P less than 0.0001. On the other hand, in no case were differences in ABP levels in normal and ectopic testes in bilateral ectopic, unilateral ectopic and normal male rats significant. Also, epididymal heads and tails on the descended side of unilateral ectopic rats demonstrated no significant difference when compared to corresponding tissues in normal male siblings.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen receptors in the brain of neonatal normal male and androgen insensitive rats.

Androgen binding was investigated in the cytosol of brains from neonatal normal and tfm rats using sucrose gradient and charcoal assay. The neonatal normal rat brain contains androgen receptors which sediment at 8S in a sucrose gradient at low ionic strength and at 4S in the presence of 0.5M KC1. These receptors have a high affinity (Kd = 1.2 X 10(-9)M) for dihydrotestosterone (DHT), with a binding capacity of 7.3 X 10(-15) moles/mg cytosol protein. By contrast, there is very little, if any, high affinity androgen receptors in the neonatal tfm rat brain. Apparently, metabolism of testosterone does not affect androgen binding in the neonatal rat brain. The presence of these receptors and the occurrence of aromatization in the brain of neonatal rats are discussed in relation to their possible roles in sexual differentiation of the brain.

Risk of respiratory syncytial virus infection for infants from low-income families in relationship to age, sex, ethnic group, and maternal antibody level.

The risk for hospitalization with respiratory syncytial virus infection during the first year of life was about five per 1,000 live births per year for infants born to low-income families in Houston from 1975 to 1979. The risk varied depending upon the intensity of the epidemic for a given season, the month of birth of the infant, and the level of passively acquired maternal antibody at the time of birth. Over 80% of the children hospitalized were less than 6 months of age; thus, most were born during the six months preceding the peak of RS virus activity. The neutralizing antibody titers in cord sera of 68 infants with culture-proven infections before 6 months of age were significantly lower than those of 575 randomly selected cord samples of infants born during the same period. The level of antibody at the time of birth was directly correlated with age at the time of infection. In addition, infants with more severe illnesses had lower levels of antibody in serum collected near onset of illness than did infants with milder illnesses. These observations demonstrate protection against RS infection in early infancy that is correlated with the level of maternal antibody, but it is not known if this protection is mediated directly by the passively acquired antibody or by some other mechanism.

Structural and functional factors related to testicular neoplasia in feminized rats.

Testicular tumors in King-Holtzman hybrid rats with testicular feminization (tfm) were seen as firm, rounded masses of tissue consisting of Leydig cells, myoid cells, and fibroblast-like cells. The cytoplasm of Leydig cells contained well-developed smooth endoplasmic reticulum, pleomorphic mitochondria with numerous cristae, and many lipid droplets. Mitochondria were numerous and varied in size and shape. Their cristae were in the form of tubules, and lipid-like inclusions were frequently seen in the mitochondrial matrix. Lysosomes, rough endoplasmic reticulum, and Golgi bodies were also scattered in the cytoplasm. An in vitro study showed that more testosterone was produced in the tumor than in the testes of rats with tfm; however, the amount in both was less than normal. Testicular tumor-bearing rats with tfm exhibited slightly higher levels of plasma testosterone than did non-tumor-bearing animals with tfm. Levels in both were significantly higher than normal. Testicular tumor cells growing in culture medium supplemented with luteinizing hormone (LH) contained more protein and synthesized more androgen and DNA than did those growing in culture medium without LH. Observed under the scanning and transmission electron microscopes, the LH-stimulated cells had well-developed cytoplasmic organelles and inclusions and surface specializations such as numerous microvilli, large blebs, and other microextensions. They adhered well to the glass surface. These results indicated that Leydig cells in testicular tumors of rats with tfm had morphologic characteristics of steroid-producing cells. In addition these cells were capable of producing steroids, and this capability was enhanced by the presence of LH.

Effects of testosterone and oestrogen on serum prolactin in the androgen-insensitive rat.

Serum prolactin levels in intact, castrated, and castrated adrenalectomized normal and male pseudohermaphrodite (Tfm) rats were compared before and after administering testosterone oenanthate and oestradiol benzoate. Without steroids, castration alone and castration plus adrenalectomy effected a drop in prolactin titres which was greater in the castrated-adrenalectomized rats. Although testosterone did not raise the prolactin titres in any of the animals studied, oestrogen raised them far above normal in all. The fall in prolactin following castration and castration + adrenalectomy could be the result of removal of organs that were producing oestrogen.

Epidemiologic observations of influenza B virus infections in Houston, Texas, 1976-1977.

Influenza B virus infections were documented in Houston, Texas, in 726 patients with febrile respiratory illnesses who presented to representative primary care facilities during the 1976-1977 respiratory disease season. This epidemic followed a "herald wave" of illness associated with influenza B during the preceding spring. Over one-half the virus isolates were from children aged 5-19 years, and school absenteeism rates indicated that about 40 per cent of the students in the Houston area were ill enough to miss school during the epidemic. The rapid rise in the number of cases among students after the school holiday recess demonstrated the importance of school attendance for the rapid dissemination of influenza viruses. During the later phase of the epidemic, most of the cases were preschool children and adults. In addition to disease of the respiratory tract, the epidemic was accompanied by cases of Reye's syndrome at a rate expected for an urban area.

Ultrastructural and biochemical characteristics of Leydig cells from newborn androgen-insensitive rats.

Leydig cells of testis of newborn pseudohermaphrodite (tfm) rats have an ultrastructure similar to that of the normal, containing well developed organelles and inclusions. The cytoplasm is filled with smooth endoplasmic reticulum forming a network of interconnected tubules. Lipid droplets are surrounded by cisternae of smooth endoplasmic reticulum and are in close association with pleomorphic mitochondria. Many of the latter are cup-shaped and have tubular cristae and intramitochondrial dense bodies. Essentially, these are characteristics of normal Leydig cells. Accordingly, the production of testosterone by testes from newborn tfm rats is the same as that by testes from normal newborns and adults. However, it is significantly higher than that by testes of tfm adults. Also, the plasma testosterone levels of newborn tfm rats are the same as in the normal newborn, but lower than in normal adults and much lower than in adult tfm animals. Thus, since in the tfm rat the morphology of Leydig cells, androgen production, and maintenance of plasma levels of testosterone are normal in the newborn, but become abnormal with advancing age, it appears that defective androgen action rather than insufficient androgen production is the cause of male pseudohermaphroditism.