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This incident prompted the USPHS to click here undertake a large surveillance study of INH-associated liver injury.46 Nearly 14?000 persons taking INH were enrolled at 21 health departments across the USA. One hundred seventy-four (1.3% of persons enrolled) probable and possible cases of INH hepatotoxicity were identified, including eight deaths. Factors associated with INH hepatotoxicity were age (>35?years old) and daily alcohol consumption. A meta-analysis of six studies (including the Capitol Hill investigation, the USPHS surveillance study and the Eastern European IUAT trial) that had a combined total of more than 38?000 persons treated with INH found that overall 0.6% developed hepatotoxicity.81 The percentage of persons with hepatotoxicity varied by study from 0 to 2.9%. However, more recent observational studies suggest that the occurrence of INH hepatotoxicity can be substantially lower when routine clinical monitoring for adverse effects is used. Public health clinics in Seattle (approximately 11?000 patients) and San Diego (approximately 3800 patients) reported incidences of INH-associated hepatotoxicity of 0.1% and 0.3%, respectively, with no deaths and only one hospitalization.77,78 Peripheral neuropathy, related to the inhibitory effect of INH on the function of pyridoxine metabolites, is another well-recognized adverse effect. Peripheral AG14699 neuropathy is unusual in otherwise healthy individuals ( Quetiapine and pregnant women.52,70,82 INH-associated peripheral neuropathy can be both prevented and treated by concurrent administration of pyridoxine (vitamin B6). Other rare adverse effects that have been attributed to INH include anaemia, leucopenia, seizures and a systemic lupus erythematosus-like syndrome.52,82,83 With regard to the latter, it is more common to see asymptomatic elevations in antinuclear antibody (ANA) titres than the actual lupus-like syndrome. Non-specific adverse effects seen with most medications, such as rash, nausea and fatigue, are seen more frequently.83 While the controlled trials demonstrated that INH was efficacious for the treatment of LTBI, the effectiveness of this intervention is dependent upon physicians prescribing, as well as patients accepting and completing a full course of medication. To begin with, physicians may not recommend therapy, even when it appears indicated,84,85 particularly in older patients.7 In several large-scale studies physicians did not recommend LTBI therapy to 20�C30% of patients who appeared eligible.84�C89 Subsequently, a substantial portion of patients may decline LTBI treatment when it is offered. In a retrospective study of clinics providing LTBI treatment, 123 (17.1%) of 720 patients did not accept treatment when eligible.90 A study of 259 health-care workers who were eligible for and offered an appointment to begin LTBI treatment found that 80 (30.