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We conducted a quantitative analysis of published results from more than 50 tests of polychlorinated biphenyl (PCB) effects on mink reproduction, which provided a basis for evaluating how well different methods of measuring and assessing PCB concentrations can approximate a toxicologically relevant dose for this endpoint. Several dose metrics were identified for comparison. Dietary dose metrics included the daily intake of total PCBs and the daily intake of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalence concentrations (TECs), calculated using World Health Organization toxicity equivalence factors (TEFs). Internal dose metrics included whole-body total PCBs, whole-body TECs calculated using World Health Organization TEFs, and whole-body TECs calculated using alternative TEFs specifically identified for internal dose assessment. Accounting for the bioaccumulative potential (i.e., internal dose) of ingested PCBs proved to be more important than accounting for the concentrations of dioxin-like PCB congeners in explaining the observed variation in reproductive success. This was true regardless of whether internal doses were estimated from dietary data based on homolog concentrations (whole-body total PCBs) or congener concentrations (whole-body TECs). For each of the PCB dose metrics, a range of toxicity reference values is identified based on the species-specific PCB toxicity database compiled for this evaluation.

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Although it is accepted that trifluoroacetic acid (TFA) can cause suppression of an analyte during LC/MS analysis, this paper presents a relatively sensitive gradient method that uses a TFA mobile phase for the improved quantification of small, polar drug-like compounds. The described method was developed in a discovery drug metabolism and pharmacokinetics (DMPK) laboratory for the screening measurement of compound concentrations to calculate PK parameters and CNS exposure of compounds from a chemical series that had poor chromatography under generic methods using formic acid mobile phase. The samples were collected by a Culex automated sampling unit, and the plasma proteins were precipitated by a Tecan robot in 96-well plates. After centrifugation, the supernatant was removed, dried down using a SPE-Dry unit, and the samples were reconstituted in aqueous buffer on the robot. The samples were analyzed on an Agilent LC/MSD using a 5-min gradient on a 5 cm phenyl column. No additional steps, such as the "TFA-fix", were necessary. Although sample batches were analyzed over 6h, no drift or degradation of signal was observed. The improved chromatography resulted in a method that was selective, rugged, and had a dynamic range from 5 to 20,000 nM, which was sufficient to quantitate low volume, serial plasma samples collected out to 8 h postdose.

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After being diagnosed with a melanoma, an 18-year-old woman developed anaphylactic shock following an intracutaneous injection of patent blue during a sentinel lymph node biopsy procedure. Intracutaneous allergy tests revealed positive reactions with patent blue (Bleu patenté V 'Guerbet') as well as with several anaesthetics and morphine. It was concluded that patent blue was the most probable causative agent for the anaphylactic reaction and that the possibility of such a reaction should be taken into consideration during sentinel node procedures. After a few days the operation was completed under epidural anaesthesia with technetium Tc 99m sulphur colloid being used to detect the sentinel node.

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Contaminant bioavailability via digestive exposure was examined for 18 species of marine benthic invertebrates, using incubation of digestive fluids with sediments that were spiked with either radiolabeled benzo-[a]-pyrene (BaP) or zinc. Interphyletic trends in contaminant solubilization were compared with measures of digestive biochemistry, including enzyme activities, surfactancy, pH, and fluid phase organic carbon, amino acids, and lipids. Contaminant solubilization ranged from values equal to that of a seawater control to as much as an order of magnitude higher but were lower than those obtained with commonly used chemical extractants. Digestive fluids from echinoderms and a cnidarian tended to be relatively weak, those from polychaetes and echiurans were relatively strong, and those from taxa such as sipunculans and mollusks were intermediate. These trends correlated strongly with concentrations or activities of digestive biochemicals but not with pH. These correlations are consistent with previous work on mechanisms of digestive solubilization of polycyclic aromatic hydrocarbons (PAH) and metals, though strong covariance among digestive parameters does not allow this approach to be used for identification of specific mechanism(s).

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This study tests whether an outreach educational program tailored to institutional specific patient care practices would improve the quality of care delivered to mechanically ventilated intensive care unit (ICU) patients in rural hospitals. The study was conducted as a randomized control trial using 20 rural Iowa hospitals as the unit of analysis. Twelve randomly selected hospitals received an outreach educational program. After review of the medical records of eligible patients, a multidisciplinary team of intensive care unit specialists from an academic medical center delivered an educational program with content specific to the findings and capacity of the hospital. The outcome measures included patient care processes, patient morbidity and mortality outcomes, and resource use. Results indicated that the outreach program significantly improved many patient care processes (lab work, nursing, dietary management, ventilator management, ventilator weaning). The program marginally reduced hospital ventilator days. Both total length of stay and ICU length of stay fell markedly in the intervention group (by an average of 3.2 and 2.1 d, respectively), while the control group fell only 0.6 and 0.3 d, respectively. However, these effects did not reach statistical significance. Unfortunately, the program had no detectable effects on the clinical outcomes of mortality or nosocomial events. We conclude that an outreach program of this type can effectively improve processes of care in rural ICUs. However, improving processes of care may not always translate into improvement of specific outcomes.

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An assay was developed for the quantification of anastrozole [2,2'-[5-(1H-1,2,4-triazol-1-ymethyl)-1,3-phenylene]bis(2-++ +methylpropiononitrile)] in human plasma using liquid-liquid extraction. Anastrozole and an internal standard were chromatographed and detected by gas chromatography with electron capture detection, using a combination temperature-pressure program. The range of the assay is 3 to 100 ng/ml. Anastrozole was quantified by comparing its peak area to that of an internal standard. A cross-validation of this assay was also successfully performed between several laboratories.

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OBJECTIVE: To examine the relationship between patient characteristics, processes of care, and risk of hospital mortality in rural intensive care units (ICU). DESIGN: Retrospective data analysis of ICU patients admitted to 19 rural Iowa hospitals between 1992 and 1994. SETTING: ICUs in rural Iowa hospitals. PATIENTS: ICU patients treated on mechanical ventilators meeting eligibility criteria. MEASUREMENTS AND MAIN RESULTS: Patient age (odds ratio = 1.03, p < .01), a higher Acute Physiology and Chronic Health Evaluation II score (odds ratio = 1.06, p < .01), and a longer pre-ICU length of stay (odds ratio = 1.14, p < .05) were associated with a higher risk of death. Seven processes of care were examined (i.e., laboratory work, nursing assessment, stress ulcer protection, immobilization protection, nutritional management, ventilator management, and weaning). Considerable variation was observed between hospitals in performance of processes of care. Controlling for patient characteristics, better performance in ulcer protection (odds ratio = 0.1, p < .05) and ventilator management (odds ratio = 0.03, p < .05) were related to lower risk of mortality. A model incorporating both patient characteristics and processes of care achieved higher predictive accuracy than a model containing only patient characteristics (area under the receiver operating characteristic curve: 0.80 vs. 0.70, p < .01). CONCLUSIONS: Most of the variation in mortality was explained by differences in patient physiologic and demographic characteristics at ICU admission. After adjusting for patient characteristics, better performance in some processes of care would have significant impact on reducing risk of mortality.

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OBJECTIVE: To identify determinants of missed medication doses in hospitalized patients. DESIGN: A prospective study of 63,031 medication doses was performed. Missed doses were detected through active surveillance. To analyze the potential impact of missed antibiotic doses, we performed a retrospective cohort study of adults with bacterial meningitis. SETTING: A general medical ward and an intensive-care unit in a tertiary-care hospital. PATIENTS: Adult inpatients. RESULTS: There were 906 missed doses (1.4% of all doses). The risk of missing a dose increased directly with the number of daily doses per patient (P<.01). An individual dose was more likely to be missed if the medication was short-acting than if it was long-acting (odds ratio, 1.4; 95% confidence interval, 1.2 to 1.6). Antimicrobials were the most frequently ordered short-acting agents and the most frequently missed class of drug. Patient absences from the floor were common, but only 3% of missed doses occurred during a scheduled absence. A survey revealed that nurses thought missed doses were the predictable result of a system involving multiple personnel and procedural steps. Missed doses were not associated with increased mortality in the cohort study. CONCLUSIONS: Missed doses correlated strongly with the number of daily doses. Efforts to decrease missed doses should focus on minimizing the number of daily doses and streamlining the administration system.

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OBJECTIVE: To determine the importance of procedure-related complications on a general medical service. DESIGN: A retrospective cohort study with one-to-one matching. Complications were identified through chart review by nurse-technicians using standard definitions. SETTING: The internal medicine service of a 900-bed university hospital. PATIENTS: One hundred seven cases with noninfectious, procedure-related complications and 107 closely matched controls who underwent the same procedures without complication. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mortality rate was 28% for cases compared with 11% for controls, resulting in an excess mortality rate of 17% (p = 0.02). Cases who survived to discharge had an excess length of stay of seven days (p = 0.001). The excess cost per case was $12,913. Importantly, median reimbursement was only $2,064 higher for cases than for controls. Adjusting for age and APACHE II (severity of illness) score, procedure-related complications were associated with a 3.4-fold increase in the relative risk of in-hospital mortality (95% CI: 1.5 to 7.7). Surveillance data were useful in directing quality improvement activities that resulted in a 66% reduction in the rate of pneumothorax following thoracentesis. CONCLUSIONS: Procedure-related complications were associated with prolonged and expensive hospitalization and were a marker for patients at high risk for in-hospital mortality. Programs to reduce complications on the general medical service have an enormous potential to benefit both patients and hospitals.

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