Firefighters' urinary concentrations of VOC metabolites after controlled-residential and training fire responses.

INTRODUCTION: Firefighters are exposed to volatile organic compounds (VOCs) during structural fire responses and training fires, several of which (e.g., benzene, acrolein, styrene) are known or probable carcinogens. Exposure studies have found that firefighters can absorb chemicals like benzene even when self-contained breathing apparatus (SCBA) are worn, suggesting that dermal absorption contributes to potentially harmful exposures. However, few studies have characterized VOC metabolites in urine from firefighters. OBJECTIVES: We quantified VOC metabolites in firefighters' urine following live firefighting activity across two field studies. METHODS: In two separate controlled field studies, spot urine was collected before and 3 h after firefighters and firefighter students responded to simulated residential and training fires. Urine was also collected from instructors from the training fire study before the first and 3 h after the last training scenario for each day (instructors led three training scenarios per day). Samples were analyzed for metabolites of VOCs to which firefighters may be exposed. RESULTS: In the residential fire study, urinary metabolites of xylenes (2MHA), toluene (BzMA), and styrene (MADA) increased significantly (at 0.05 level) from pre- to post-fire. In the training fire study, MADA concentrations increased significantly from pre- to post-fire for both firefighter students and instructors. Urinary concentrations of benzene metabolites (MUCA and PhMA) increased significantly from pre- to post-fire for instructors, while metabolites of xylenes (3MHA+4MHA) and acrolein (3HPMA) increased significantly for firefighter students. The two highest MUCA concentrations measured post-shift from instructors exceeded the BEI of 500 µg/g creatinine. CONCLUSIONS: Some of the metabolites that were significantly elevated post-fire are known or probable human carcinogens (benzene, styrene, acrolein); thus, exposure to these compounds should be eliminated or reduced as much as possible through the hierarchy of controls. Given stringent use of SCBA, it appears that dermal exposure contributes in part to the levels measured here.

Characterizing exposures to flame retardants, dioxins, and furans among firefighters responding to controlled residential fires.

Firefighters may encounter items containing flame retardants (FRs), including organophosphate flame retardants (OPFRs) and polybrominated diphenyl ethers (PBDEs), during structure fires. This study utilized biological monitoring to characterize FR exposures in 36 firefighters assigned to interior, exterior, and overhaul job assignments, before and after responding to controlled residential fire scenarios. Firefighters provided four urine samples (pre-fire and 3-h, 6-h, and 12-h post-fire) and two serum samples (pre-fire and approximately 23-h post-fire). Urine samples were analyzed for OPFR metabolites, while serum samples were analyzed for PBDEs, brominated and chlorinated furans, and chlorinated dioxins. Urinary concentrations of diphenyl phosphate (DPhP), a metabolite of triphenyl phosphate (TPhP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), a metabolite of tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and bis(2-chloroethyl) phosphate (BCEtP), a metabolite of tris(2-chloroethyl) phosphate (TCEP), increased from pre-fire to 3-hr and 6-hr post-fire collection, but only the DPhP increase was statistically significant at a 0.05 level. The 3-hr and 6-hr post-fire concentrations of DPhP and BDCPP, as well as the pre-fire concentration of BDCPP, were statistically significantly higher than general population levels. BDCPP pre-fire concentrations were statistically significantly higher in firefighters who previously participated in a scenario (within the past 12 days) than those who were responding to their first scenario as part of the study. Similarly, firefighters previously assigned to interior job assignments had higher pre-fire concentrations of BDCPP than those previously assigned to exterior job assignments. Pre-fire serum concentrations of 2,3,4,7,8-pentachlorodibenzofuran (23478-PeCDF), a known human carcinogen, were also statistically significantly above the general population levels. Of the PBDEs quantified, only decabromodiphenyl ether (BDE-209) pre- and post-fire serum concentrations were statistically significantly higher than the general population. These results suggest firefighters absorbed certain FRs while responding to fire scenarios.

Frailty assessment and risk prediction by GRACE score in older patients with acute myocardial infarction.

BACKGROUND: Risk prediction after myocardial infarction is often complex in older patients. The Global Registry of Acute Coronary Events (GRACE) model includes clinical parameters and age, but not frailty. We hypothesised that frailty would enhance the prognostic properties of GRACE. METHODS: We performed a prospective observational cohort study in two independent cardiology units: the Royal Infirmary of Edinburgh, UK (primary cohort) and the South Yorkshire Cardiothoracic Centre, Sheffield, UK (external validation). The study sample included 198 patients ≥65 years old hospitalised with type 1 myocardial infarction (primary cohort) and 96 patients ≥65 years old undergoing cardiac catheterisation for myocardial infarction (external validation). Frailty was assessed using the Clinical Frailty Scale (CFS). The GRACE 2.0 estimated risk of 12-month mortality, Charlson comorbidity index and Karnofsky disability scale were also determined for each patient. RESULTS: Forty (20%) patients were frail (CFS ≥5). These individuals had greater comorbidity, functional impairment and a higher risk of death at 12 months (49% vs. 9% in non-frail patients, p < 0.001). The hazard of 12-month all-cause mortality nearly doubled per point increase in CFS after adjustment for age, sex and comorbidity (Hazard Ratio [HR] 1.90, 95% CI 1.47-2.44, p < 0.001). The CFS had good discrimination for mortality by Receiver Operating Characteristic (ROC) curve analysis (Area Under the Curve [AUC] 0.81, 95% CI 0.72-0.89) and enhanced the GRACE estimate (AUC 0.86 vs. 0.80 without CFS, p = 0.04). At existing GRACE thresholds, the CFS resulted in a Net Reclassification Improvement (NRI) of 0.44 (95% CI 0.28-0.60, p < 0.001), largely through reductions in risk estimates amongst non-frail patients. Similar findings were observed in the external validation cohort (NRI 0.46, 95% CI 0.23-0.69, p < 0.001). CONCLUSIONS: The GRACE score overestimated mortality risk after myocardial infarction in these cohorts of older patients. The CFS is a simple guided frailty tool that may enhance prediction in this setting. These findings merit evaluation in larger cohorts of unselected patients. TRIAL REGISTRATION: Clinicaltrials.gov; NCT02302014 (November 26th 2014, retrospectively registered).

Firefighters' absorption of PAHs and VOCs during controlled residential fires by job assignment and fire attack tactic.

To better understand the absorption of combustion byproducts during firefighting, we performed biological monitoring (breath and urine) on firefighters who responded to controlled residential fires and examined the results by job assignment and fire attack tactic. Urine was analyzed for metabolites of polycyclic aromatic hydrocarbons (PAHs) and breath was analyzed for volatile organic compounds (VOCs) including benzene. Median concentrations of PAH metabolites in urine increased from pre-firefighting to 3-h post firefighting for all job assignments. This change was greatest for firefighters assigned to attack and search with 2.3, 5.6, 3.9, and 1.4-fold median increases in pyrene, phenanthrene, naphthalene, and fluorene metabolites. Median exhaled breath concentrations of benzene increased 2-fold for attack and search firefighters (p < 0.01) and 1.4-fold for outside vent firefighters (p = 0.02). Compared to interior attack, transitional attack resulted in 50% less uptake of pyrene (p = 0.09), 36% less uptake phenanthrene (p = 0.052), and 20% less uptake of fluorene (p < 0.01). Dermal absorption likely contributed to firefighters' exposures in this study. Firefighters' exposures will vary by job assignment and can be reduced by employing a transitional fire attack when feasible.

Firefighters' and instructors' absorption of PAHs and benzene during training exercises.

INTRODUCTION: Training fires may constitute a major portion of some firefighters' occupational exposures to smoke. However, the magnitude and composition of those exposures are not well understood and may vary by the type of training scenario and fuels. OBJECTIVES: To understand how structure fire training contributes to firefighters' and instructors' select chemical exposures, we conducted biological monitoring during exercises involving combustion of pallet and straw and oriented strand board (OSB) or the use of simulated smoke. METHODS: Urine was analyzed for metabolites of polycyclic aromatic hydrocarbons (PAHs) and breath was analyzed for volatile organic compounds (VOCs) including benzene. RESULTS: Median concentrations of nearly all PAH metabolites in urine increased from pre-to 3-hr post-training for each scenario and were highest for OSB, followed by pallet and straw, and then simulated smoke. For instructors who supervised three trainings per day, median concentrations increased at each collection. A single day of OSB exercises led to a 30-fold increase in 1-hydroxypyrene for instructors, culminating in a median end-of-shift concentration 3.5-fold greater than median levels measured from firefighters in a previous controlled-residential fire study. Breath concentrations of benzene increased 2 to 7-fold immediately after the training exercises (with the exception of simulated smoke training). Exposures were highest for the OSB scenario and instructors accumulated PAHs with repeated daily exercises. CONCLUSIONS: Dermal absorption likely contributed to the biological levels as the respiratory route was well protected. Training academies should consider exposure risks as well as instructional objectives when selecting training exercises.

Field evaluation of onsite near real-time monitors for surface contamination by 5-fluorouracil.

OBJECTIVES: In order to produce near real-time onsite results to detect surface contamination by antineoplastic drugs, the National Institute for Occupational Safety and Health developed monitors for 5-fluorouracil, which use surface wiping and lateral flow immunoassay for measurement. The monitors were tested in the laboratory to assess the sensitivity of detection on laboratory-produced contaminated surfaces. A field evaluation to assess the capability of the monitors to make measurements in healthcare workplaces was carried out in collaboration with a medical device company and the results are presented in this report. METHODS: The 5-fluorouracil monitor was evaluated in areas where oncology drugs were prepared and administered to patients at five different hospitals. The levels of contamination measured with the monitors were compared to levels measured with liquid chromatography-tandem mass spectrometry. RESULTS: The 5-fluorouracil values measured with the liquid chromatography-tandem mass spectrometry ranged from 0 to over 200,000 ng/100 cm2. Measurements by the 5-fluorouracil monitors in the range 10-100 ng/100 cm2 correlated with the liquid chromatography-tandem mass spectrometry. Receiver operating characteristic curves developed for the data indicated that a positive limit of 22 ng/100 cm2 would give an acceptable level of false-positives while retaining most true-positive samples. If the liquid chromatography-tandem mass spectrometry measured greater than 100 ng/100 cm2, then the monitors also measured levels greater than 100 ng/100 cm2 for the majority of samples. CONCLUSION: The data indicate that there are many areas in hospitals that are contaminated with 5-fluorouracil and the monitors will be useful in identifying this contamination.

Contamination of firefighter personal protective equipment and skin and the effectiveness of decontamination procedures.

Firefighters' skin may be exposed to chemicals via permeation/penetration of combustion byproducts through or around personal protective equipment (PPE) or from the cross-transfer of contaminants on PPE to the skin. Additionally, volatile contaminants can evaporate from PPE following a response and be inhaled by firefighters. Using polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) as respective markers for non-volatile and volatile substances, we investigated the contamination of firefighters' turnout gear and skin following controlled residential fire responses. Participants were grouped into three crews of twelve firefighters. Each crew was deployed to a fire scenario (one per day, four total) and then paired up to complete six fireground job assignments. Wipe sampling of the exterior of the turnout gear was conducted pre- and post-fire. Wipe samples were also collected from a subset of the gear after field decontamination. VOCs off-gassing from gear were also measured pre-fire, post-fire, and post-decon. Wipe sampling of the firefighters' hands and neck was conducted pre- and post-fire. Additional wipes were collected after cleaning neck skin. PAH levels on turnout gear increased after each response and were greatest for gear worn by firefighters assigned to fire attack and to search and rescue activities. Field decontamination using dish soap, water, and scrubbing was able to reduce PAH contamination on turnout jackets by a median of 85%. Off-gassing VOC levels increased post-fire and then decreased 17-36 min later regardless of whether field decontamination was performed. Median post-fire PAH levels on the neck were near or below the limit of detection (< 24 micrograms per square meter [µg/m2]) for all positions. For firefighters assigned to attack, search, and outside ventilation, the 75th percentile values on the neck were 152, 71.7, and 39.3 µg/m2, respectively. Firefighters assigned to attack and search had higher post-fire median hand contamination (135 and 226 µg/m2, respectively) than other positions (< 10.5 µg/m2). Cleansing wipes were able to reduce PAH contamination on neck skin by a median of 54%.

Phase 2 Randomised Controlled Trial and Feasibility Study of Future Care Planning in Patients with Advanced Heart Disease.

Future Care Planning (FCP) rarely occurs in patients with heart disease until close to death by which time the potential benefits are lost. We assessed the feasibility, acceptability and tested a design of a randomised trial evaluating the impact of FCP in patients and carers. 50 patients hospitalised with acute heart failure or acute coronary syndrome and with predicted 12 month mortality risk of >20% were randomly allocated to FCP or usual care for 12 weeks upon discharge and then crossed-over for the next 12 weeks. Quality of life, symptoms and anxiety/distress were assessed by questionnaire. Hospitalisation and mortality events were documented for 6 months post-discharge. FCP increased implementation and documentation of key decisions linked to end-of-life care. FCP did not increase anxiety/distress (Kessler score -E 16.7 (7.0) vs D 16.8 (7.3), p = 0.94). Quality of life was unchanged (EQ5D: E 0.54(0.29) vs D 0.56(0.24), p = 0.86) while unadjusted hospitalised nights was lower (E 8.6 (15.3) vs D 11.8 (17.1), p = 0.01). Qualitative interviews indicated that FCP was highly valued by patients, carers and family physicians. FCP is feasible in a randomised clinical trial in patients with acute high risk cardiac conditions. A Phase 3 trial is needed urgently.

Detection and measurement of surface contamination by multiple antineoplastic drugs using multiplex bead assay.

OBJECTIVES: Contamination of workplace surfaces by antineoplastic drugs presents an exposure risk for healthcare workers. Traditional instrumental methods to detect contamination such as liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) are sensitive and accurate but expensive. Since immunochemical methods may be cheaper and faster than instrumental methods, we wanted to explore their use for routine drug residue detection for preventing worker exposure. METHODS: In this study we examined the feasibility of using fluorescence covalent microbead immunosorbent assay (FCMIA) for simultaneous detection and semi-quantitative measurement of three antineoplastic drugs (5-fluorouracil, paclitaxel, and doxorubicin). The concentration ranges for the assay were 0-1000 ng/ml for 5-fluorouracil, 0-100 ng/ml for paclitaxel, and 0-2 ng/ml for doxorubicin. The surface sampling technique involved wiping a loaded surface with a swab wetted with wash buffer, extracting the swab in storage/blocking buffer, and measuring drugs in the extract using FCMIA. RESULTS: There was no significant cross-reactivity between these drugs at the ranges studied indicated by a lack of response in the assay to cross analytes. The limit of detection (LOD) for 5-fluorouracil on the surface studied was 0.93 ng/cm(2) with a limit of quantitation (LOQ) of 2.8 ng/cm(2), the LOD for paclitaxel was 0.57 ng/cm(2) with an LOQ of 2.06 ng/cm(2), and the LOD for doxorubicin was 0.0036 ng/cm(2) with an LOQ of 0.013 ng/cm(2). CONCLUSION: The use of FCMIA with a simple sampling technique has potential for low cost simultaneous detection and semi-quantitative measurement of surface contamination from multiple antineoplastic drugs.

Detection of 5-fluorouracil surface contamination in near real time.

OBJECTIVES: Contamination of workplace surfaces by antineoplastic drugs presents an exposure risk for healthcare workers. Traditional instrumental methods to detect contamination such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) are sensitive and accurate but expensive and incapable of producing results in real time. This limits their utility in preventing worker exposure. We are currently developing monitors based on lateral flow immunoassay that can detect drug contamination in near real time. In this report, we describe the laboratory performance of a 5-fluorouracil (5-FU) monitor. METHODS: The monitor was evaluated by spiking ceramic, vinyl, composite, stainless steel, and glass surfaces of 100 cm(2) area with 5-FU masses of 0, 5, 10, 25, 50, and 100 ng. The surface was sampled with a wetted cotton swab, the swab was extracted with buffer, and the resulting solution was applied to a lateral flow monitor. Two ways of evaluating the response of these monitors were used: an electronic method where a lateral flow reader was used for measuring line intensities, and a visual method where the intensity of the test line was visually compared to the control line. RESULTS: The 5-FU monitor is capable of detecting 10 ng/100 cm(2) (0.1 ng/cm(2)) using the electronic reader and 25 ng/100 cm(2) (0.25 ng/cm(2)) using the visual comparison method for the surfaces studied. The response of the monitors was compared to LC-MS/MS results for the same samples for validation and there was good correlation of the two methods but some differences in absolute response, especially at higher spiking levels for the surface samples.

Enhanced performance of methamphetamine lateral flow cassettes using an electronic lateral flow reader.

Surface contamination from methamphetamine in meth labs continues to be a problem. We had previously developed a lateral flow assay cassette for field detection of methamphetamine contamination that is commercially available and has been used by a number of groups to assess contamination. This cassette uses the complete disappearance of the test line as an end point for detection of 50 ng/100 cm2 of methamphetamine contamination for surface sampling with cotton swabs. In the present study, we further evaluate the response of the cassettes using an electronic lateral flow reader to measure the intensities of the test and control lines. The cassettes were capable of detecting 0.25 ng/ml for calibration solutions. For 100 cm2 ceramic tiles that were spiked with methamphetamine and wiped with cotton-tipped wooden swabs wetted in assay/sampling buffer, 1 ng/tile was detected using the reader. Semi-quantitative results can be produced over the range 0-10 ng/ml for calibration solutions and 0-25 ng/tile for spiked tiles using either a 4-parameter logistic fit of test line intensity versus concentration or spiked mass or the ratio of the control line to the test line intensity fit to concentration or spiked mass. Recovery from the tiles was determined to be about 30% using the fitted curves. Comparison of the control line to the test line was also examined as a possible visual detection end point and it was found that the control line became more intense than the test line at 0.5 to 1 ng/ml for calibration solutions or 1 to 2 ng/tile for spiked tiles. Thus the lateral flow cassettes for methamphetamine have the potential to produce more sensitive semi-quantitative results if an electronic lateral flow reader is used and can be more sensitive for detection if the comparison of the control line to the test line is used as the visual end point.

Future Care Planning for patients approaching end-of-life with advanced heart disease: an interview study with patients, carers and healthcare professionals exploring the content, rationale and design of a randomised clinical trial.

OBJECTIVE: To explore the optimal content and design of a clinical trial of an end-of-life intervention for advanced heart disease with patients, carers and healthcare professionals. DESIGN: Qualitative interview and focus group study. SETTING: Community and hospital-based focus groups and interviews. PARTICIPANTS: Stable community-dwelling patients, informal carers (PC, n=15) and primary and secondary care based healthcare professionals (HCP, n=11). RESULTS: PC highlighted fragmentation of services and difficulty in accessing specialist care as key barriers to good care. They felt that time for discussion with HCP was inadequate within current National Health Service (NHS) healthcare systems. HCP highlighted uncertainty of prognosis, explaining mortality risk to patients and switching from curative to palliative approaches as key challenges. Patient selection, nature of the intervention and relevance of trial outcomes were identified by HCP as key challenges in the design of a clinical trial. CONCLUSIONS: PC and HCP expressed a number of concerns relevant to the nature and content of an end-of-life intervention for patients with advanced heart disease. The findings of this study are being used to support a phase II randomised clinical trial of Future Care Planning in advanced heart disease.

A pilot study of workplace dermal exposures to cypermethrin at a chemical manufacturing plant.

Exposure during the manufacture of pesticides is of particular concern due to their toxicity and because little is known about worker exposure, since most studies have focused on end-use application within agriculture or buildings. Even though dermal exposure can be expected to dominate for pesticides, little is known about workplace dermal exposures or even appropriate methods for their assessment. The current study begins to address this gap by evaluating alternative methods for assessing dermal exposure at a chemical manufacturing plant. For this pilot study, eight workers were recruited from a U.S. plant that produced the pesticide cypermethrin. Exposure was evaluated using three approaches: (1) survey assessment (questionnaire), (2) biological monitoring, and (3) workplace environmental sampling including ancillary measurements of glove contamination (interior and exterior). In each case, cypermethrin was quantified by enzyme-linked immunosorbent assay (ELISA). Environmental measurements identified two potential pathways of cypermethrin exposure: glove and surface contamination. Workplace exposure was also indicated by urine levels (specific gravity adjusted) of the parent compound, which ranged from 35 to 253 µg/L (median of 121 µg/L) with no clear trend in levels from pre- to post-shift. An exploratory analysis intended to guide future studies revealed a positive predictive association (Spearman correlation, p ≤ 0.10) between post-shift urine concentrations and a subset of survey questions evaluating worker knowledge, attitudes, and perceptions (KAP) of workplace dermal hazards, i.e., personal protective equipment self-efficacy, and inverse associations with behavior belief and information belief scales. These findings are valuable in demonstrating a variety of dermal exposure methods (i.e., behavioral attributes, external contamination, and biomarker) showing feasibility and providing measurement ranges and preliminary associations to support future and more complete assessments. Although these pilot data are useful for supporting design and sample size considerations for larger exposure and health studies, there is a need for validation studies of the ELISA assay for quantification of cypermethrin and its metabolites in urine.

Measurement of multiple drugs in urine, water, and on surfaces using fluorescence covalent microbead immunosorbent assay.

There are a range of applications that require the measurement of multiple drugs such as urine analysis, drug determination in water, and screening for drug contamination on surfaces. Some of the procedures used such as enzyme-linked immunosorbent assay (ELISA) are simple but can only determine one drug at a time, and others such as GC-MS or LC-MS are complex, time-consuming, and expensive. In this study, fluorescence covalent microbead immunosorbent assay (FCMIA) was investigated as a simple method for the measurement of multiple drugs simultaneously in three matrices: diluted urine, water, and on surfaces. Five different drugs of abuse or their metabolites (methamphetamine, caffeine, benzoylecgonine (a metabolite of cocaine), tetrahydrocannabinol (THC), the active ingredient in marijuana, and oxycodone) were studied over the range 0-15 ng/ml. There was no measureable cross-reactivity among the drugs at the concentrations studied. Urine dilutions from 1/50 to 1/2.5 were studied and dilutions less than 1/20 had a significant effect on the methamphetamine assay but limited effects on the benzoylecgonine and oxycodone assays and almost no effect on the THC assay. For assays performed in 1/20 urine dilution, water, and diluted surface sampling buffer, least detectable doses (LDD) were 1 ng/ml or less for the drugs. Surfaces spiked with drugs were sampled with swabs wetted with surface sampling buffer and recoveries were linear over the range 0-100 ng/100 cm(2) surface loading for all drugs. FCMIA has potential to be used for the measurement of multiple drugs in the matrices studied.

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

The association of nonalcoholic steatohepatitis and tamoxifen in patients with breast cancer.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a form of liver damage that can progress to cirrhosis. NASH is associated with obesity and diabetes. The condition also may be associated with some medications, including tamoxifen. Early case reports and small series have documented NASH in patients who received tamoxifen. METHODS: The records of patients registered in the St. Vincent Hospital Cancer Registry of Green Bay Wisconsin from January 1, 1992 to December 31, 2000 were reviewed. RESULTS: In total, 1105 patients with breast cancer were evaluated for NASH, and 24 cases of NASH were documented (2.2%). Seven patients had NASH before their diagnosis of breast cancer, and 17 patients developed NASH after their diagnosis of breast cancer. In multivariate analysis, the factors associated with NASH were tamoxifen use (odds ratio [OR], 8.2; 95% confidence interval [CI], 1.06-63.72), body mass index (BMI) (OR, 1.13; 95% CI, 1.06-1.20), and age (OR, 95% CI, 0.91-0.99). NASH improved after tamoxifen was stopped. After discontinuation of tamoxifen, transaminase levels returned to normal in 14 of 16 patients. CONCLUSIONS: NASH was present in 24 of 1105 patients with breast cancer (2.2%). Seven patients had NASH before they were diagnosed with breast cancer, and 17 patients developed NASH after their diagnosis. NASH was associated with the use of tamoxifen and improved when tamoxifen was stopped.

Evaluation of body mass index, pre-vaccination serum progesterone levels and anti-anthrax protective antigen immunoglobulin G on injection site adverse events following anthrax vaccination in women.

BACKGROUND: In 2002, CDC initiated the Anthrax Vaccination Program (AVP) to provide voluntary pre-exposure anthrax vaccination for individuals at high risk for exposure to Bacillus anthracis spores. The AVP offered an opportunity to investigate hypothesized reasons for a reported gender difference in injection site adverse events (AEs) following anthrax vaccine adsorbed (AVA). OBJECTIVES: To evaluate in women the impact of body mass index (BMI), pre-vaccination serum progesterone levels, and pre-vaccination anti-anthrax protective antigen immunoglobulin G concentrations (anti-PA IgG) on the occurrence of AEs following subcutaneous AVA vaccination. METHODS: Participants' BMI was determined at enrollment. Also, pre-vaccination blood samples were assayed for serum progesterone and anti-PA IgG. Post-vaccination solicited AEs were recorded by participants using a 4-day diary card. RESULTS: Obese group had an elevated risk for arm soreness. Decreased pre-vaccination serum progesterone level was associated with arm swelling. Increased pre-vaccination anti-PA IgG was associated with itching on the arm; and within the obese group, was associated with arm swelling, lump or knot, redness, soreness, and warmth. CONCLUSIONS: In AVA vaccinated women, obesity was associated with arm soreness and decreased pre-vaccination serum progesterone levels were associated with increased rate of arm swelling. Increased pre-vaccination anti-PA IgG may be associated with an increased frequency of itching on the arm, and in obese women, may increase the occurrence of arm swelling, lump or knot, redness, and warmth. Administering AVA according to a woman's menstrual phase may reduce the occurrence of certain injection site reactions.

Rapid point-of-care test to detect broad ranges of protective antigen-specific immunoglobulin G concentrations in recipients of the U.S.-licensed anthrax vaccine.

Currently, there is no routine monitoring of an immune response to the anthrax vaccine. Simple on-site tests are needed to evaluate the antibody response of anthrax-vaccinated individuals in the Armed Forces and others at high risk. Using a prototype lateral flow assay (LFA) (R. E. Biagini, D. L. Sammons, J. P. Smith, B. A. MacKenzie, C. A. F. Striley, J. E. Snawder, S. A. Robertson, and C. P. Quinn, Clin. Vaccine Immunol. 13:541-546, 2006), we investigated the agreement between a validated anthrax protective antigen (PA) immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and the LFA for 335 unvaccinated and vaccinated subjects. We also investigated the performance of the LFA under the following conditions: thermal shock (i.e., thermal cycling between temperature extremes), high temperature/high relative humidity, high temperature/low relative humidity, and low temperature/low relative humidity. With the anti-PA ELISA used as a standard, the LFA was shown to be optimally diagnostic at 11 microg/ml anti-PA-specific IgG. At this concentration, the LFA specificity and sensitivity were 98% (95% confidence interval [CI], 97% to 100%) and 92% (CI, 88% to 97%), respectively. Receiver operating characteristic curve analysis yielded an area under the curve value of 0.988 (CI, 0.976 to 1.00), suggesting that the LFA is an extremely accurate diagnostic test. For < or = 4 or > or = 50 microg/ml PA-specific IgG, the LFA results for each environmental condition were identical to those obtained in the laboratory. These data indicate that this rapid point-of-care test would be a feasible tool in monitoring the serological antibody responses of individuals that have been vaccinated against anthrax.