Growth hormone use in children with idiopathic short stature

OBJECTIVE: To review the indication, pharmacology, pharmacokinetics, efficacy, and adverse effects of recombinant human growth hormone in children with idiopathic short stature (ISS). DATA SOURCES: A MEDLINE search (1966-December 2003) was performed using the key words human growth hormone, somatropin, Humatrope, normal children, somatrem, and idiopathic short stature. Food and Drug Administration Advisory Committee Meeting minutes were also reviewed. STUDY SELECTION AND DATA EXTRACTION: The data presented in this review were obtained from published literature, abstracts presented at scientific meetings, and information on file with the manufacturer. Additional articles from these sources were also identified. Current issues of pediatric and endocrinology journals were reviewed for the most recent articles. Articles only addressing the use of growth hormone in normal, healthy children were used. DATA SYNTHESIS: Somatropin is indicated for use in children with ISS. Studies have shown modest benefit to final height achieved and, at the doses used for ISS, there have been no adverse effects associated with somatropin. Many questions still exist, however, concerning the most appropriate age to initiate treatment and duration of treatment. There are also many ethical concerns surrounding patient selection criteria and potential for increased off-label use. CONCLUSIONS: Growth hormone has been found to have modest efficacy in improving final height in children with ISS. The specific patient population likely to achieve maximal benefit, optimal dosage regimens, and the long-term adverse effects of extended duration of therapy are unknown.     

Disparities in smoking cessation between African Americans and Whites: 1990-2000

OBJECTIVES: We examined disparities in smoking cessation rates between African Americans and Whites from 1990 through 2000. METHODS: We performed an analysis of smoking cessation with data from the National Health Interview Surveys of 30660 African Americans and 209828 Whites, 18 to 64 years old, with adjustment for covariates in multiple logistic regression models. RESULTS: Whites were significantly more likely than African Americans to be former smokers, and this disparity in the quit ratio persisted from 1990 through 2000. After adjustment for covariates, disparities were substantially reduced especially among women. Among former smokers, African Americans were significantly more likely than Whites to have quit successfully within the past 10 years. CONCLUSIONS: Statistical adjustment for covariates reduces African American-White disparities in quit ratios, and recent cessation patterns suggest possible future reductions in disparities.     

Rifapentine: its role in the treatment of tuberculosis

OBJECTIVE: To review the pharmacokinetics, efficacy, adverse effects, and cost of the newest antitubercular drug, rifapentine. DATA SOURCES: A MEDLINE search using key terms such as rifapentine, rifampin, isoniazid, Mycobacterium tuberculosis, and pyrazinamide was conducted for the time period 1966-November 1998. STUDY SELECTION: Animal data were used for basic information and human studies were selected for inclusion if they were randomized, controlled studies assessing efficacy, or if they were single- or multiple-dose studies assessing the pharmacokinetics of rifapentine. Background articles on the pathophysiology of tuberculosis and cost of care and noncontrolled studies assessing drug interactions were also included. DATA SYNTHESIS: Compared with an oral solution, the relative bioavailability of rifapentine is 70% following oral admninistration of tablets. Food increased bioavailability by 55%. Rifapentine accumulated significantly in human macrophages and its elimination half-life was longer than that of rifampin. Comparative studies of rifapentine and rifampin in humans during intensive- and continuation-phase treatment of tuberculosis suggest that at currently accepted doses, rifapentine was slightly less effective than rifampin. The most significant drug interaction with rifapentine involves indinavir: the maximum concentration and AUC of indinavir are reduced by 55% and 70%, respectively, when rifapentine is coadministered with indinavir. Adverse events of rifapentine may occur less frequently at the currently recommended 600-mg dose as compared with rifampin; however, the difference was not statistically significant. If only drug costs were evaluated during the six-month treatment of tuberculosis, rifapentine is more expensive than rifampin. CONCLUSIONS: Rifapentine can be administered twice weekly during the intensive phase of tuberculosis treatment and then once weekly during the continuation phase of treatment. This may improve patient adherence over some other treatments and possibly reduce costs of treatment by preventing development of resistant tubercular strains due to nonadherence. Rifapentine is well tolerated, with most patients experiencing adverse effects at a similar rate as rifampin. Rifapentine induces cytochrome P450 somewhat less than rifampin, although few drug interaction studies have been done with rifapentine. Its efficacy at the currently approved dosage of 600 mg may be slightly lower than that of rifampin. Studies are needed to determine if equal or greater efficacy can be achieved with higher doses of rifapentine. Rifampin is less expensive than rifapentine. Further pharmacoeconomic studies are needed to evaluate costs of relapse and failure in patients receiving these agents.     

Management of botulism

OBJECTIVE: To provide a concise review of the presentation and treatment of botulism. DATA SOURCES: Searches of MEDLINE (1966-November 2001), tertiary references, and public and government Internet sites were conducted. STUDY SELECTION: All articles and additional references from those articles were thoroughly evaluated. DATA SYNTHESIS: Clostridium botulinum toxin blocks acetylcholine release in a dose-dependent fashion, resulting in acute symmetric diplopia, dysarthria, dysphonia, dysphagia, and possible neurologic sequelae despite the route of exposure (i.e., food-borne, wound, intestinal, inhalation). Disease secondary to genetically engineered C. botulinum may differ from that of inadvertent exposure. Present treatment is primarily supportive care, respiratory support, rapid decontamination, and antitoxin administration (i.e., trivalent, pentavalent, heptavalent antitoxin). Early initiation of antitoxin limits the extent of paralysis, but does not reverse it. CONCLUSIONS: Supportive care and the use of antitoxin have been effective in the treatment of botulism from food-borne, intestinal, and wound exposure. However, the effectiveness of antitoxin in the treatment of inhaled C. botulinum has not been proven.