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.     

Serum concentrations of oestradiol-17beta, progesterone, relaxin and chorionic gonadotrophin during blastocyst implantation in natural pregnancy cycle and in embryo transfer cycle in the rhesus monkey

The present study was undertaken to assess the temporal association between the profiles of serum concentrations of oestradiol-17beta, progesterone, chorionic gonadotrophin (CG) and relaxin in pregnancies established naturally, and after embryo transfer, as well as in failed pregnancies in rhesus monkeys. In naturally mated cycles (group 1) a conception rate of 75% was obtained. In group 1, the mean day of CG detection in serum was 11.5 +/- 1.9 day post-ovulation, and for relaxin, 9.0 +/- 2.5 day post-ovulation. In group 2, embryo transfer to synchronous, non-mated surrogate recipients was performed; seven embryo transfer cycles yielded three pregnancies which were allowed to continue to term and normal infants were delivered. In embryo transfer cycles the mean day of CG detection was 14.8 +/- 1.8 day post- ovulation, and for relaxin, 11.4 +/- 2.6 day post-ovulation. A delay of about 3 days was observed in the appearance in circulation of CG (P < 0.05) and also of relaxin (P < 0.05) between natural mated and embryo transfer conception cycles. Significant differences (P < 0.05 for progesterone and P < 0.03 for oestradiol) were obtained for the areas under the curves for progesterone and oestradiol between days 12 and 16 in conception cycles compared with failed pregnancies. These data provide the first observation of the normal hormonal signals associated with maternal recognition of transferred embryos during the peri- implantation period, and suggest that the use of such an experimental primate embryo transfer model may help to elucidate components of maternal and embryonic signal-response mechanisms during embryo implantation.      

A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides

Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonradomized studies have suggested that early aggressive therapy may improve the prognosis in this usually fatal disease. We studied 103 patients with mycosis fungoides, who, after complete staging, were randomly assigned to receive either combination therapy, consisting of 3000 cGy of electron-beam radiation to the skin combined with parenteral chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine (n = 52) or sequential topical treatment (n = 51). The prognostic factors were well balanced in the two groups. Combined therapy produced considerable toxicity: 12 patients required hospitalization for fever and transient neutropenia, 5 had congestive heart failure, and 2 were later found to have acute nonlymphocytic leukemia. Patients receiving combined therapy had a significantly higher rate of complete response, documented by biopsy, than patients receiving conservative therapy (38 percent vs. 18 percent; P = 0.032). After a median follow-up of 75 months, however, there was no significant difference between the treatment groups in disease-free or overall survival. We conclude that early aggressive therapy with radiation and chemotherapy does not improve the prognosis for patients with mycosis fungoides as compared with conservative treatment beginning with sequential topical therapies.     

Females experiencing sexual and drug vulnerabilities are at elevated risk for HIV infection among youth who use injection drugs

OBJECTIVES: To compare sociodemographic, drug-related, and sexual risk variables between young (13-24 years of age) and older (> or =25 years of age) injection drug users (IDUs); and to determine HIV prevalence and associated risk factors for HIV infection among young IDUs. METHODS: Data were collected through the Vancouver Injection Drug Users Study (VIDUS). To date, over 1400 Vancouver area IDUs have been enrolled and observed during follow-up. Sociodemographic, drug-related, and sexual risk variables were compared between younger and older IDUs using nonparametric methods. Mantel-Haenszel and logistic regression methods were used to compare HIV-positive and HIV-negative female youth. RESULTS: Younger injectors (N = 232) were more likely to be female; work in the sex trade; report condom use; inject heroin daily; smoke crack cocaine daily; and need help injecting. HIV prevalence at baseline among the youth was 10%. HIV prevalence was associated with female gender; history of sexual abuse; engaging in survival sex; injecting heroin daily; injecting speedballs (a mixture of heroin and cocaine) daily; and having numerous lifetime sexual partners. CONCLUSION: Our data show that HIV positivity among young IDUs is concentrated among females engaged in dual sexual and drug-related risk exposure categories. Over half the HIV-positive youth were Aboriginal (a classification used by the federal government in Canada to include native peoples of all ethnic groups). Targeted interventions that take into account sexual and drug risk for young female and Aboriginal peoples are urgently needed.     

Response of tanycytes of rat median eminence to intraventricular administration of colchicine and vinblastine.

The effects of colchicine and vinblastine on tanycytes of the rat median eminence have been studied using the electron microscope. Colchicine and vinblastine were administered by intraventricular cannulation into the third ventricle and demonstrated distinct morphological effects on tanycyte microtubules. Highest drug doses administered were 50.0 mug in 5.0 mul of saline initially, followed by an additional 50.0 mug of these agents infused in a volume of 13.0 mul saline over an hour. Colchicine treatment resulted in the formation of large crystalloids within tanycytes, coincident with the disappearance of microtubules, all along the ventricular surface. Nonetheless the tanycytes appeared able to maintain a continuous, tight lining, as in controls, although some crystalloids were observed beneath the ventricular surface, either within tanycyte processes or within neuronal processes. Vinblastine treatment also resulted in the formation of identical crystalloids but at highest doses thoroughly destroyed the tanycyte lining of the median eminence and exposed cellular elements below the surface to the drug. Portal capillaries approaching the ventricular surface were generally free of any signs of drug response to either colchicine or vinblastine.