Survey of guidelines and current practices for safe handling of antineoplastic and other hazardous drugs used in 24 countries.

PURPOSE: A survey of guidelines and current practices was conducted to examine the safe handling procedures for antineoplastic and other hazardous drugs that are used in 24 countries including the Americas, Europe, the Mideast, Far East, and Australia. METHODS: Subject experts were asked to complete a brief survey regarding safe handling guidelines and practices for hazardous drugs in their countries. Questions addressed practices for handling monoclonal antibodies, the use of closed-system transfer devices, medical surveillance practices, and measurements of compliance with existing guidelines. RESULTS: Responses from 37 subject experts representing 24 countries revealed considerable variation in the content and scope of safe handling guidelines and pharmacy practices among the participating countries. Guidelines in the majority of countries used the term "cytotoxics," while others referred to "hazardous" or "antineoplastic" drugs. The International Society of Oncology Pharmacy Practice standard was cited by six countries, and five cited the National Institute for Occupational Safety and Health Alert. Others cited international guidelines other than International Society of Oncology Pharmacy Practice, or they have created their own guidelines. Approximately half reported that their guidelines were mandatory under federal, state, or provincial legislation. Only 11 countries reported that monoclonal antibodies were covered in their guidelines. Closed-system drug-transfer devices are widely used, but were not specifically recommended in four countries, while one country required their use. Medical surveillance programs are in place in 20 countries, but only in The Netherlands is surveillance mandatory. Nine countries reported that they have completed recent updates or revisions of guidelines, and the measures for their adoption have been initiated. CONCLUSIONS: Although the overall goals in the participating countries were similar, the approaches taken to assure safe handling of hazardous drugs varied considerably in some cases.

The association of pipe and cigar use with cotinine levels, lung function, and airflow obstruction: a cross-sectional study.

BACKGROUND: Cigarette smoking is the major cause of chronic obstructive pulmonary disease, but studies on the contribution of other smoking techniques are sparse. OBJECTIVE: To determine whether pipe and cigar smoking was associated with elevated cotinine levels, decrements in lung function, and increased odds of airflow obstruction. DESIGN: Cross-sectional study. SETTING: Population-based sample from 6 U.S. communities. PARTICIPANTS: Men and women aged 48 to 90 years without clinical cardiovascular disease at enrollment who were part of MESA (Multi-Ethnic Study of Atherosclerosis). MEASUREMENTS: The MESA Lung Study measured spirometry according to American Thoracic Society guidelines and urine cotinine levels by immunoassay on a subsample of MESA. Pipe-years and cigar-years were calculated as years from self-reported age of starting to age of quitting (or to current age in current users) multiplied by pipe-bowls or cigars per day. RESULTS: Of 3528 participants, 9% reported pipe smoking (median, 15 pipe-years), 11% reported cigar smoking (median, 6 cigar-years), and 52% reported cigarette smoking (median, 18 pack-years). Self-reported current pipe and cigar smokers had elevated urine cotinine levels compared with never-smokers. Pipe-years were associated with decrements in FEV(1), and cigar-years were associated with decrements in the FEV(1)-FVC ratio. Participants who smoked pipes or cigars had increased odds of airflow obstruction whether they had also smoked cigarettes (odds ratio, 3.43 [95% CI, 1.75 to 6.71]; P < 0.001) or not (odds ratio, 2.31 [CI, 1.04 to 5.11]; P = 0.039) compared with participants with no smoking history. LIMITATION: Cross-sectional design. CONCLUSION: Pipe and cigar smoking increased urine cotinine levels and was associated with decreased lung function and increased odds of airflow obstruction, even in participants who had never smoked cigarettes. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute, National Institutes of Health.

A pilot respiratory health assessment of nail technicians: symptoms, lung function, and airway inflammation.

BACKGROUND: Recent surveys suggest nail technicians, particularly artificial nail applicators, have increased respiratory symptoms and asthma risk. METHODS: We examined lung function (n = 62) and a marker of airway inflammation, i.e., exhaled nitric oxide (ENO) (n = 43), in a subset of nail technician and control participants in a pilot health assessment. RESULTS: Bivariate analysis of technicians demonstrated that job latency was inversely correlated with FEV1 percent predicted (FEV1PP) (r = -0.34, P = 0.03) and FVCPP (r = -0.32, P = 0.05). Acrylic gel contact hours were inversely correlated with FEV1PP (r = -0.38, P = 0.02) and FVCPP (r = -0.47, P = 0.003). Current smoking was inversely and significantly (P

Latex specific IgE: performance characteristics of the IMMULITE 2000 3gAllergy assay compared with skin testing.

BACKGROUND: In the absence of a US Food and Drug Administration (FDA)-cleared latex skin testing reagent, in vitro tests remain important for the diagnosis of latex allergy. OBJECTIVE: To evaluate the performance characteristics of IMMULITE 2000 3gAllergy (Immulite), a third-generation, FDA-cleared, continuous random-access immunoanalyzer, for the quantification of latex specific IgE. METHODS: Stored serum samples (N = 201) from patients classified as having positive or negative latex puncture skin test results were measured for latex specific IgE levels using Immulite, and these data were compared with historical results from 3 second-generation, FDA-cleared IgE antilatex assays (AlaSTAT [Ala], AutoCAP [CAP], and HY*TEC enzyme immunoassay [HT]). RESULTS: The diagnostic performances of the CAP, Ala, and Immulite assays (> or = 0.35 kU/L cutoff value) were equivalent in sensitivity and specificity (P > .05). The HT assay (> or = 0.05 kU/L cutoff value) was more sensitive and less specific (P < .05). Immulite (> or = 0.10 kU/L cutoff value) had greater sensitivity than Ala and CAP and greater specificity than HT (P < .05 for both). Diagnostic efficiency was greater for Immulite than for CAP, Ala, and HT (P < .05). CONCLUSIONS: The Immulite system is superior in diagnostic performance, especially at the 0.10 kU/L or greater cutoff level, for the diagnosis of latex allergy compared with older, second-generation assays. Immulite still misclassifies 15.5% of puncture skin test-positive individuals as negative for latex specific IgE. Compared with second-generation assays, Immulite represents a technological advance, with enhanced speed and less operator intervention.

Rapid, sensitive, and specific lateral-flow immunochromatographic device to measure anti-anthrax protective antigen immunoglobulin g in serum and whole blood.

Evidence from animals suggests that anti-anthrax protective antigen (PA) immunoglobulin G (IgG) from vaccination with anthrax vaccine adsorbed (AVA) is protective against Bacillus anthracis infection. Measurement of anti-PA IgG in human sera can be performed using either enzyme-linked immunosorbent assay or fluorescent covalent microsphere immunoassay (ELISA) (R. E. Biagini, D. L. Sammons, J. P. Smith, B. A. MacKenzie, C. A. Striley, V. Semenova, E. Steward-Clark, K. Stamey, A. E. Freeman, C. P. Quinn, and J. E. Snawder, Clin. Diagn. Lab. Immunol. 11:50-55, 2004). Both these methods are laboratory based. We describe the development of a rapid lateral-flow immunochromatographic assay (LFIA) test kit for the measurement of anti-PA IgG in serum or whole-blood samples (30-microl samples) using colloidal gold nanoparticles as the detection reagent and an internal control. Using sera from 19 anthrax AVA vaccinees (anti-PA IgG range, 2.4 to 340 microg/ml) and 10 controls and PA-supplemented whole-blood samples, we demonstrated that the LFIA had a sensitivity of approximately 3 microg/ml anti-PA IgG in serum and approximately 14 microg/ml anti-PA IgG in whole blood. Preabsorption of sera with PA yielded negative anti-PA LFIAs. The diagnostic sensitivity and specificity of the assay were 100% using ELISA-measured anti-PA IgG as the standard. This kit has utility in determining anti-PA antibody reactivity in the sera of individuals vaccinated with AVA or individuals with clinical anthrax.

Evaluation of the prevalence of antiwheat-, anti-flour dust, and anti-alpha-amylase specific IgE antibodies in US blood donors.

BACKGROUND: Asthma in bakery workers is one of the most frequently occurring forms of occupational asthma in the world. Experience from other countries has shown the prevalence of sensitization (IgE) to bakery-associated allergens (BAAs) (wheat [W], flour dust [FD], alpha-amylase [AA]) in bakery workers to be 5% to 53%, whereas the prevalence in nonoccupationally exposed individuals was estimated to be 1.2% to 6.4%. OBJECTIVE: To estimate the prevalence of BAA sensitization by measuring BAA specific IgE in the residual serum tubes of volunteer blood donors. METHODS: Serum samples from 534 volunteer blood donors were measured for anti-W, anti-FD, and anti-AA specific IgE antibodies (in duplicate) using the AlaSTAT microplate assay. Samples with BAA IgE concentrations of 0.35 kU/L or greater were considered positive. RESULTS: Nineteen of 530 serum samples (3.6%; 95% confidence interval [CI], 3.3%-3.9%) were positive for W (range, 0.38-3.61 kU/L), whereas 31 of 534 (5.8%; 95% CI, 5.3%-6.3%) were positive for FD (range, 0.35-2.34 kU/L) and 5 of 529 (1.0%; 95% CI, 0.9%-1.1%) were positive for AA (range, 0.38-1.59 kU/L). Thirteen serum samples were positive for both W and FD; 1 sample each was positive for W and AA and FD and AA. CONCLUSIONS: The prevalence of IgE sensitization in serum samples from a relatively large unselected population of volunteer blood donors is 1.0% for AA, 3.6% for W, and 5.8% for FD, which agrees well with data from other countries for sensitization prevalence rates for nonoccupationally exposed individuals.

Comparison of a multiplexed fluorescent covalent microsphere immunoassay and an enzyme-linked immunosorbent assay for measurement of human immunoglobulin G antibodies to anthrax toxins.

Recently, the Centers for Disease Control and Prevention reported an accurate, sensitive, specific, reproducible, and quantitative enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to Bacillus anthracis protective antigen (PA) in human serum (C. P. Quinn, V. A. Semenova, C. M. Elie et al., Emerg. Infect. Dis. 8:1103-1110, 2002). The ELISA had a minimum detectable concentration (MDC) of 0.06 microgram/ml, which, when dilution adjusted, yielded a whole-serum MDC of 3.0 micro g of anti-PA IgG per ml. The reliable detection limit (RDL) was 0.09 microgram/ml, while the dynamic range was 0.06 to 1.7 microgram/ml. The diagnostic sensitivity of the assay was 97.6% and the diagnostic specificity was 94.2% for clinically verified cases of anthrax. A competitive inhibition anti-PA IgG ELISA was also developed to enhance the diagnostic specificity to 100%. We report a newly developed fluorescence covalent microbead immunosorbent assay (FCMIA) for B. anthracis PA which was Luminex xMap technology. The FCMIA MDC was 0.006 microgram of anti-PA IgG per ml, the RDL was 0.016 microgram/ml, and the whole-serum equivalent MDC was 1.5 micrograms/ml. The dynamic range was 0.006 to 6.8 microgram/ml. Using this system, we analyzed 20 serum samples for anti-PA IgG and compared our results to those measured by ELISA in a double-masked analysis. The two methods had a high positive correlation (r2 = 0.852; P < 0.001). The FCMIA appears to have benefits over the ELISA for the measurement of anti-PA IgG, including greater sensitivity and speed, enhanced dynamic range and reagent stability, the use of smaller sample volumes, and the ability to be multiplexed (measurement of more than one analyte simultaneously), as evidenced by the multiplexed measurement in the present report of anti-PA and anti-lethal factor IgG in serum from a confirmed clinical anthrax infection.

Method for simultaneous measurement of antibodies to 23 pneumococcal capsular polysaccharides.

We describe a fluorescent covalent microsphere immunoassay (FCMIA) method for the simultaneous (multiplexed) measurement of immunoglobulin G (IgG) antibodies to 23 pneumococcal capsular polysaccharide (PnPS) serotypes present in the pneumococcal polysaccharide vaccine (PPV23) licensed by the Food and Drug Administration, i.e., PnPSs 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F. In addition, the assay incorporates an internal control that allows for contemporaneous evaluation of the effectiveness of pneumococcal cell wall polysaccharide (C-PS) preadsorption and a second control of PnPS 25 (which is not present in any polysaccharide or conjugate vaccine), which can be used to evaluate interassay reproducibility (useful for pre- versus postvaccination studies). The FCMIA was standardized with U.S. reference antipneumococcal serotype standard serum 89S-2. Preadsorption of 89S-2 with each PnPS and C-PS yielded homologous inhibition for serotypes 1, 6B, 9N, 9V, 11A, 12F,14, 15B, 18C, 19A, 19F, 20, 22F, 25, and 33F; heterologous inhibition for serotypes 9V, 10A, 11A, 12F, 15B, 17F, 20, and 23F; and neither homologous nor heterologous inhibition for serotypes 2, 3, 4, and 5. The minimum detectable concentrations for the 24 multiplexed (PnPS and C-PS) FCMIAs ranged from 20 pg/ml for PnPS 3 to 600 pg/ml for PnPS 14. The PnPS FCMIA method has numerous benefits over enzyme-linked immunosorbent assays commonly used to measure anti-PnPS-specific IgG levels, including increased speed, smaller sample volumes, equivalent or better sensitivity, and increased dynamic range.

Biological monitoring for selected herbicide biomarkers in the urine of exposed custom applicators: application of mixed-effect models.

Metabolites and/or parent compounds of the herbicides atrazine, alachlor, metolachlor, cyanazine and the 2-ethylhexyl ester of 2,4-dichlorophenoxyacetic acid (2,4-D) were measured in the urine of 15 custom applicators who each provided from five to seven 24 h urine samples during a 6 week period (n = 87). Each applicator provided a pre-season urine sample and a reference population (n = 46) provided first-morning urine samples. Urinary biomarkers were measured by either immunoassay or gas chromatography. During the spraying season, the geometric mean amount of alachlor mercapturate equivalents (eq.), atrazine eq., 2,4-D and metolachlor mercapturate eq. excreted in 24 h was 17, 19, 110 and 22 nmol, respectively. Mixed-effect models were used to determine predictors of the amount of atrazine eq. and 2,4-D excreted in 24 h. The specific days of herbicide spraying associated with increased biomarker excretion varied for the two analytes, and included one or more days prior to urine collection. This confirms the importance of collecting covariate information on day(s) most relevant to the biomarker of interest. The within-worker variance component, expressed as a geometric standard deviation ((W)GSD range: 2.5-2.9), was substantially larger than the between-worker component ((B)GSD range: 1.3-1.5) for the modeled biomarkers. Alachlor mercapturate eq. and metolachlor mercapturate eq. were detected in more than half of the applicator pre-season urine samples. All biomarkers were detected infrequently in the reference population. Evaluation of non-spray exposure determinants was limited by inclusion of prior day spraying, adjustment for time and the small sample size.