Tuberculosis prevention: cost-effectiveness analysis of isoniazid chemoprophylaxis

Isoniazid chemoprophylaxis is not recommended for all persons infected with tubercle bacilli. Because of the small but significant risk of isoniazid hepatotoxicity, chemoprophylaxis is reserved for only those at the highest risk of tuberculosis activation. To evaluate this policy, we performed a cost-effectiveness analysis of isoniazid chemoprophylaxis for two populations with positive tuberculin skin tests: recent tuberculin converters, who are at high risk for activation, and older tuberculin reactors, who have a low risk for activation and for whom chemoprophylaxis is not now recommended. The cost-effectiveness ratios found were stable, despite wide variations in model assumptions and probability estimates. For high-risk tuberculin reactors, chemoprophylaxis resulted in net medical care monetary savings, extended life expectancy, and fewer fatal illnesses. For low-risk tuberculin reactors, chemoprophylaxis resulted in positive, but small, health effects. Because the cost to gain these positive effects were also small, the resulting cost-effectiveness ratios were reasonable and in the realm of accepted prevention strategies: $12,625 to gain one year of life and $35,011 to avert one death. These findings suggest that the current policy is too restrictive and that many in the large population of low-risk tuberculin reactors should be considered for isoniazid chemoprophylaxis.     

Interactions between epidermal growth factor-mediated autocrine regulation and linoleic acid-stimulated growth of a human prostate cancer cell line.

Human prostate cancer (PC) cell lines possess epidermal growth factor (EGF) receptors and secrete EGF-related polypeptides. We used an EGF receptor-blocking antibody (anti-EGF.R) to demonstrate a functional autocrine loop, as well as the interaction between this and the effects of linoleic acid (LA), an omega-6 fatty acid, on PC cell growth. The anti-EGF.R competed effectively with [125I]EGF for receptors on DU145 PC cells, and on a high-passage DU145 variant (DU145M); when added to the culture medium, it suppressed both DU145 and DU145M cell growth in a dose-dependent manner. LA, a precursor for eicosanoid synthesis, had little effect on DU145 cell growth rate but stimulated DU145M growth in a concentration-related manner over a range of 0.25-2.0 micrograms/ml. anti-EGF.R (10(-9) M) caused suppression of LA-stimulated growth of DU145M cells in serum-free medium, which was prevented by the addition of 2 nM EGF. We conclude that an EGF.R-mediated autocrine loop is involved in PC cell growth regulation and that at least one site of action may be the synthesis of eicosanoids from their LA precursor.     

The relationship among receptive and expressive vocabulary, listening comprehension, pre-reading skills, word identification skills, and reading comprehension by children with reading disabilities.

PURPOSE: Some researchers (F. R. Vellutino, F. M. Scanlon, & M. S. Tanzman, 1994) have argued that the different domains comprising language (e.g., phonology, semantics, and grammar) may influence reading development in a differential manner and at different developmental periods. The purpose of this study was to examine proposed causal relationships among different linguistic subsystems and different measures of reading achievement in a group of children with reading disabilities. METHODS: Participants were 279 students in 2nd to 3rd grade who met research criteria for reading disability. Of those students, 108 were girls and 171 were boys. In terms of heritage, 135 were African and 144 were Caucasian. Measures assessing pre-reading skills, word identification, reading comprehension, and general oral language skills were administered. RESULTS: Structural equation modeling analyses indicated receptive and expressive vocabulary knowledge was independently related to pre-reading skills. Additionally, expressive vocabulary knowledge and listening comprehension skills were found to be independently related to word identification abilities. CONCLUSION: Results are consistent with previous research indicating that oral language skills are related to reading achievement (e.g., A. Olofsson & J. Niedersoe, 1999; H. S. Scarborough, 1990). Results from this study suggest that receptive and expressive vocabulary knowledge influence pre-reading skills in differential ways. Further, results suggest that expressive vocabulary knowledge and listening comprehension skills facilitate word identification skills.     

Interobserver variability in neonatal cranial ultrasonography

The reliability of cranial ultrasound diagnosis in the premature neonate was examined using data from an ongoing multicentre study of the epidemiology and long-term consequences of neonatal brain haemorrhage. First week ultrasound films (obtained at 4 hours, 24 hours and 7 days) from 60 study subjects were randomly selected for independent review by two groups of experienced interpreters, and results were recorded separately for observations (i.e. presence or absence of an abnormal echodense area on a film) and interpretations (i.e. presence or absence of haemorrhage or ventricular dilatation) in each hemisphere. Because of deaths in the first week of life, the total number of films examined was 138. Concordance on the presence or absence of an abnormal echodensity was examined for each individual film for three areas of interest: the germinal matrix, the ventricles and the parenchyma. Concordance on the presence or absence of haemorrhage or ventricular dilatation was examined only for the seventh-day film, or the final film prior to death. Finally, concordance was analysed with the diagnostic interpretations grouped into categories thought to differ prognostically for long-term outcome. In general, concordance was poorest for germinal matrix lesions and best for parenchymal lesions. Concordance was lower for observations made on each individual film than it was for interpretation of the final film in each case. Fifty-five of 60 cases (92%) were assigned to the same major prognostic category by both readers. Ultrasound review conferences were held periodically and there was evidence that concordance in ultrasound reading and interpretation improved during the course of the study.     

Predicting death from coronary heart disease using a questionnaire

The ten-year coronary heart disease (CHD) mortality is reported for 18,322 male civil servants aged 40 to 64 according to questionnaire responses at entry into the Whitehall study. In all 1714 died, 723 from CHD. The predictive power of the questionnaire was examined with a view to its use as a screening tool in population studies. In predicting death from coronary heart disease the greatest specificity (true negative rate) was achieved with men reporting both angina (A) and a history of severe chest pain (possible myocardial infarction, PMI). This strategy (A plus PMI) achieved a specificity of 99% but a sensitivity (true positive rate) of only 7%. In contrast, in men reporting angina and/or PMI, specificity was 90% and sensitivity 29%. If this 'and/or' algorithm was extended to include the report of dyspnoea, diabetes, and/or attending a primary care physician with heart disease or hypertension, then specificity was still 85%, but sensitivity increased to 44%. This combination (11 questions in all) is therefore recommended for screening purposes. Identifying and excluding those who favour positive answers ('yes-set' responders), using questions such as the effect of weather on breathing, led to small increases in specificity but relatively large falls in sensitivity. Among subjects reporting chest pain, those who also complained of non-specific symptoms experienced only half the mortality of those with none of these additional complaints.     

Occult prostatic carcinoma metastatic to the medial canthal area. Diagnosis by immunohistochemistry

A 91-year-old man developed a mass in the right medial canthal and lacrimal sac region, which was found histopathologically to be a poorly differentiated neoplasm. The results of a complete systemic evaluation, including urologic consultation, rectal examination, bone scan, and determination of serum acid phosphatase level, were normal. In spite of the negative evaluation for prostatic carcinoma, immunohistochemical studies using immunoperoxidase stains for prostatic-specific antigen demonstrated that the lacrimal sac tumor was metastatic carcinoma from an occult primary neoplasm in the prostate gland. The presence of tumor in the prostate gland was then confirmed by a needle biopsy. Modern immunohistochemical techniques are particularly valuable in the diagnosis of selected ophthalmic tumors in which the diagnosis cannot be determined by routine diagnostic techniques.