Does it matter what you call it? A randomized trial of language used to describe palliative care services.

INTRODUCTION: Integration of palliative care into oncology practice remains suboptimal. Misperceptions about the meaning of palliative care may negatively impact utilization. PURPOSE: We assessed whether the term and/or description of palliative care services affected patient views. METHODS: 2x2 between-subject randomized factorial telephone survey of 169 patients with advanced cancer. Patients were randomized into one of four groups that differed by name (supportive care vs. palliative care) and description (patient-centered vs. traditional). Main outcomes (0-10 Likert scale) were patient understanding, impressions, perceived need, and intended use of services. RESULTS: When compared to palliative care, the term supportive care was associated with better understanding (7.7 vs. 6.8; p = 0.021), more favorable impressions (8.4 vs. 7.3; p = 0.002), and higher future perceived need (8.6 vs. 7.7; p = 0.017). There was no difference in outcomes between traditional and patient-centered descriptions. In adjusted linear regression models, the term supportive care remained associated with more favorable impressions (p = 0.003) and higher future perceived need (p = 0.022) when compared to palliative care. CONCLUSIONS: Patients with advanced cancer view the name supportive care more favorably than palliative care. Future efforts to integrate principles of palliative medicine into oncology may require changing impressions of palliative care or substituting the term supportive care.

Mercury compounds reduce photosynthesis by plankton.

Concentrations of organomercurial fungicides as low as 0.1 part per billion in water reduced photosynthesis and growth in laboratory cultures of one species of marine diatom and several natural phytoplankton communities from Florida lakes. The acute toxicity of mercury compounds to phytoplankton is dependent on the chemical nature of the mercury compound and on cell concentrations.

Effect of changing NAVA levels on peak inspiratory pressures and electrical activity of the diaphragm in premature neonates.

BACKGROUND: Neurally adjusted ventilator assist (NAVA) uses electrical activity of the diaphragm (Edi) to provide patient-directed ventilatory support. The NAVA level determines the proportional amount of ventilatory support. Systematically increasing NAVA level initially increases peak inspiratory pressure (PIP) while maintaining a constant Edi until a breakpoint (BrP) is reached. Further increases in NAVA level reduce the Edi, while the PIP plateaus. This study was performed to establish whether premature neonates have intact neural feedback systems allowing them to have a BrP. METHOD: NAVA level was increased by 0.5 cm H2O µV(-1) every 3 min from 0.5 to 4.0 cm H2O µV(-1). PIP, Edi, mean blood pressure, heart rate, respiratory rate, oxygen saturation and FIO2 were recorded. Statistics: Non-linear regression was done for PIP and Edi. Linear regression was done for the other variables. The data from the trials were combined by normalizing to NAVA levels above and below the BrP. RESULT: Nine neonates were studied on NAVA and 12 on non-invasive NAVA. PIP increased until the BrP was reached and then remained unchanged. Edi decreased after the BrP was reached. All other variables remained unchanged. CONCLUSION: Neonates demonstrated a BrP suggesting intact neural feedback mechanisms that may protect lungs from over distention with NAVA ventilation.

Standard error and sample size determination for estimation of probabilities based on a test variable.

A method of sample size determination for estimation of probabilities based on a test variable is presented. Applications to estimation of sensitivity and specificity of medical tests are the focus of this research, although the methods can be applied to other areas of study such as engineering reliability. Examples are given for determining sample sizes required for the classification of patients with cutaneous lupus erythematosus based on the incidence of several markers. In this example, the test variable is the number of markers present. The methodology employs a weighted average of model-based and non-model-based estimates of the probability with the weights determined by the closeness to or the confidence in the given model. Formulas and charts required for determining sample size are provided for test variables that can be modeled by the binomial, Poisson, or normal distributions, i.e., for the most commonly encountered distributions for counting events (binomial and Poisson) and for measurements (normal). However, the methods given can be applied to any distribution, including multivariate. Especially when relatively small probabilities (the rare events) are being estimated, the techniques provided assistance in safeguarding against undersampling brought on by unwarranted confidence in a test variable distribution and against oversampling required for high accuracy in non-model-based probability estimators.

Investigation of how different halos influence pin forces.

STUDY DESIGN: This study investigated the effect of the size and material of halo rings on the pin force produced at the halo pin-calvarium complex. SUMMARY OF BACKGROUND DATA: Loosening of halo pins has been a problem with using the halo-vest apparatus to stabilize cervical spine fractures. METHODS: One standard halo pin and seven different halo rings were used to test the anterior pin hole of each ring at a constant torque of 8 inch-pounds (0.9 Nm). RESULTS: Pin force fluctuated from halo to halo, and decreased as the nut was tightened. CONCLUSIONS: Identical torques applied to different halos will not guarantee the same magnitude of pin force for halo fixation.

Fairy Rings in Turf Associated with the Bird's Nest Fungus Cyathus stercoreus.

During the summer of 1998, several fairy rings with the fruiting bodies of a bird's nest fungus were observed on two greens at the University of Minnesota turf plots in St. Paul. Both greens, a 3-year-old annual bluegrass green and a 2-year-old creeping bentgrass green, were constructed of a 90% sand: 10% reed sedge peat soil mix. The fungus was identified as Cyathus stercoreus (Schwein.) de Toni (Nidulariaceae) (1). The fruiting bodies were approximately 15 mm tall and 8 mm wide. The fairy rings were irregular in shape, with a diameter of up to 50 cm, and contained up to 120 fruiting bodies per ring. On annual bluegrass, chlorotic and necrotic grass was observed at the edge of the rings in July but those damaged areas recovered in August. No symptoms were associated with the rings in creeping bentgrass. Rings were first discovered in June and early July and expanded by about 10 cm in 30 days. New fruiting bodies appeared during July and August as the rings expanded. The application of the fungicide chorothalanil did not affect the rings. This is the first report of a bird's nest fungus associated with fairy ring in turf. Reference: (1) H. J. Brodie. 1975. The Bird's Nest Fungi. University of Toronto Press, Toronto.

Modified tension band wiring of medial malleolar ankle fractures.

Twenty-two displaced medial malleolar ankle fractures that were treated surgically using the modified tension band method of Cleak and Dawson were retrospectively reviewed at an average follow-up of 25 months. The technique involves the use of a screw to anchor a figure-of-eight wire. There were no malreductions and all fractures healed. Problems with the technique included technical errors with hardware placement, medial ankle pain, and asymptomatic wire migration. Despite this, modified tension band wiring remains an acceptable method for fixation of selected displaced medial malleolar fractures. It is especially suited for small fracture fragments and osteoporotic bone.

Electrical activity of the diaphragm (Edi) values and Edi catheter placement in non-ventilated preterm neonates.

OBJECTIVE: The electrical activity of the diaphragm (Edi) reflects neural respiratory drive. Edi peak correlates with inspiratory drive and Edi minimum (Edi min) correlates with the tonic activity of the diaphragm. Edi data in non-ventilated preterm neonates have not been determined.The primary aim of this study was to determine Edi values in non-ventilated preterm neonates throughout postnatal maturation and with various types of noninvasive respiratory support. The secondary aim was to evaluate the success or complications of placement of the Edi catheter in premature neonates. STUDY DESIGN: This was a prospective observational study of non-ventilated neonates <33 weeks gestation. Data were collected weekly using an Edi catheter placed in neonates on highflow nasal cannula (HFNC), nasal cannula (NC) or room air (RA). Clinical stability was determined by measuring heart rate (HR), respiratory rate (RR) and oxygen saturation (Sats). Success and adverse events of Edi catheter placement was monitored. Statistics were obtained by analysis of variance, P<0.05 was considered significant. RESULT: Seventeen neonates were enrolled at 26 to 33 weeks postmenstrual age and studied from 1 to 10 weeks in duration. Overall Edi peak was 10.8±3.7 mcV (range 3.7 to 18.7) and Edi min was 2.8±1.1 mcV (range 0.8 to 7.6). There was no difference in Edi peak and min over postmenstrual ages within or between neonates, and no difference between those neonates on HFNC, NC or RA. HR, RR and Sats were not different over postmenstrual age or between any groups. The Edi catheter was placed successfully in 100% of these neonates. There were no adverse events noted. CONCLUSION: In clinically stable neonates, the inspiratory drive (Edi peak) and tonic activity (Edi min) do not change with postnatal maturation or with the level of noninvasive respiratory support. The Edi catheter can be placed successfully in these premature neonates. These Edi data have the potential to guide ventilatory management of premature neonates.

Prospective crossover comparison between NAVA and pressure control ventilation in premature neonates less than 1500 grams.

OBJECTIVE: Neurally adjusted ventilatory assist (NAVA) synchronizes spontaneous respiratory effort with mechanical ventilation. Electrodes detect the electrical activity of the diaphragm (Edi) and transmit this information to the ventilator, allowing the patient to determine their own respiratory rate (RR), peak pressures, and inspiratory and expiratory times in synchrony with the ventilator. The objective of this study was to evaluate if premature neonates ventilate as effectively on NAVA as compared to pressure control ventilation (PCV). STUDY DESIGN: Five ventilated neonates were enrolled (gestational age 25-29 weeks). Each neonate was ventilated on NAVA for 4 h, then switched to PCV for another 4 h. The cycle was repeated three times. Ventilatory parameters were averaged every 30 min to collect eight time points for each ventilatory mode. Data were analyzed using the mixed effects model procedure, utilizing the least-squares means (P<0.05). RESULT: When compared to PCV, neonates ventilated with NAVA had lower peak inspiratory pressures (PIP), fraction of inspired oxygen (FiO2), transcutaneous PCO2 Edi peak and RR. There was an increase in expiratory tidal volume (TV), compliance and Edi minimum. Despite lower PIP and RR, partial pressure of CO2 (PCO2) was lower when ventilated on NAVA. There was no difference in mean airway pressure. CONCLUSION: Premature neonates ventilated with NAVA required less PIP, FiO2 and RR to achieve lower PCO2 and better compliance compared with PCV.

Do-not-resuscitate orders and predictive models after intracerebral hemorrhage.

OBJECTIVE: To quantify the accuracy of commonly used intracerebral hemorrhage (ICH) predictive models in ICH patients with and without early do-not-resuscitate orders (DNR). METHODS: Spontaneous ICH cases (n = 487) from the Brain Attack Surveillance in Corpus Christi study (2000-2003) and the University of California, San Francisco (June 2001-May 2004) were included. Three models (the ICH Score, the Cincinnati model, and the ICH grading scale [ICH-GS]) were compared to observed 30-day mortality with a chi(2) goodness-of-fit test first overall and then stratified by early DNR orders. RESULTS: Median age was 71 years, 49% were female, median Glasgow Coma Scale score was 12, median ICH volume was 13 cm(3), and 35% had early DNR orders. Overall observed 30-day mortality was 42.7% (95% confidence interval [CI] 38.3-47.1), with the average model-predicted 30-day mortality for the ICH Score, Cincinnati model, and ICH-GS at 39.9% (p = 0.005), 40.4% (p = 0.007), and 53.9% (p < 0.001). However, for patients with early DNR orders, the observed 30-day mortality was 83.5% (95% CI 78.0-89.1), with the models predicting mortality of 64.8% (p < 0.001), 57.2% (p < 0.001), and 77.8% (p = 0.02). For patients without early DNR orders, the observed 30-day mortality was 20.8% (95% CI 16.5-25.7), with the models predicting mortality of 26.6% (p = 0.05), 31.4% (p < 0.001), and 41.1% (p < 0.001). CONCLUSIONS: ICH prognostic model performance is substantially impacted when stratifying by early DNR status, possibly giving a false sense of model accuracy when DNR status is not considered. Clinicians should be cautious when applying these predictive models to individual patients.

Instituting organizational learning for quality improvement through strategic planning nominal group processes.

Healthcare managers are faced with unprecedented challenges as characterized by managed care constraints, downsizing, increased client needs, and a society demanding more responsive services. Managers must initiate change for quality, efficiency, and survival. This article provides information and strategies for (a) assessing the change readiness of an organization, (b) conducting an organizational diagnosis, (c) instituting a team culture, (d) developing a change strategy, (e) integrating the strategy with a quality improvement process, and (f) identifying the leadership skills to implement organization renewal. Nominal group processes, namely, SWOT and the Search Conference, are described, and case examples are provided. The implementation strategies have been used successfully in a variety of milieus; practical advice for success is described in detail.

What is quality, who wants it, and why?

The health services literature is replete with examples of the failure of total quality management to produce significant change in organizational performance. Some authors suggest that incremental quality improvement be abandoned in favor of structural reengineering. However, these naysayers ignore the critical impact of environmental change, managed care, and customer service as primary organizational drivers that demand an enhanced focus on continuous quality improvement. Coupled with these factors is the movement towards the creation of learning organizations. At the core of any learning organization is a commitment to quality and the empowerment of employees to identify and improve quality.

Evaluation of hypothesis testing for comparing two populations using NONMEM analysis.

In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i) the ratio of mean clearance and (ii) the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations.

An evaluation of point and interval estimates in population pharmacokinetics using NONMEM analysis.

In a simulation study of the estimation of population pharmacokinetic parameters, including fixed and random effects, the estimates and confidence intervals produced by NONMEM were evaluated. Data were simulated according to a monoexponential model with a wide range of design and statistical parameters, under both steady state (SS) and non-SS conditions. Within the range of values for population parameters commonly encountered in research and clinical settings, NONMEM produced parameter estimates for CL, V, sigma CL, and sigma epsilon which exhibit relatively small biases. As the range of variability increases, these biases became larger and more variable. An important exception was bias in the estimate for sigma V which was large even when the underlying variability was small. NONMEM standard error estimates are appropriate as estimates of standard deviation when the underlying variability is small. Except in the case of CL, standard error estimates tend to deteriorate as underlying variability increases. An examination of confidence interval coverage indicates that caution should be exercised when the usual 95% confidence intervals are used for hypothesis testing. Finally, simulation-based corrections of point and interval estimates are possible but corrections must be performed on a case-by-case basis.

The formulatiion development and stability of spironolactone suspension.

The purpose of this study was to extemporaneously formulate a liquid dosage form from commercially available tablets and establish the chemical stability of the drug. A suspension of spironolactone (5mg/mL) was formulated from 25-mg spironolactone tablets. Stability-indicating, high perfpromance liquid chromatography assay procedures were used to analyze the concentration of the drug. Chemical stability was predicted using accelerated stability studies. The stability studies were conducted at four temperatures, namely 5*, 30*, and 50*, and 60*C. The spironolactone suspension showed less than 10% degradation at all four temperatures for a period of three months. It appears that the formulation may be stable for longer periods of time; however, the investigation did not extend past this timeline and no recommendation should be implied.

Comparison of tobramycin pharmacokinetics after administration by CRIS and a traditional intravenous piggyback infusion.

OBJECTIVE: To compare the administration pharmacokinetics of a 30-minute intravenous piggyback (ivpb) infusion of tobramycin with those of controlled-release infusion system (CRIS) using a 20-mL vial at rates of 60 and 120 mL/h. DESIGN: Randomized, controlled, crossover, prospective, open-label trial. SETTING: Medical college-affiliated hospital. PARTICIPANTS: Eight healthy volunteer men between the ages of 22 and 24 years weighing between 60 and 90 kg. INTERVENTIONS: Volunteers received, in random order, tobramycin sulfate 2 mg/kg i.v. on 3 occasions separated by 1 week. The drug was administered using a 50-mL ivpb infusion at 100 mL/h for 30 minutes, and with the CRIS using a 20-mL vial with flow rates of 60 mL/h for 1 hour (slow) and 120 mL/h for 1 hour (fast). MAIN OUTCOME MEASURES: Primary endpoints were area under the time-concentration curve (AUC), time to reach maximum concentration (tmax), and maximum concentration (Cmax). Secondary endpoints were elimination rate constant (ke), clearance (Cl), and half-life (t1/2). RESULTS: Six volunteers successfully completed the trial. The tmax values observed following fast CRIS and ivpb were 28 +/- 8 and 32 +/- 4 minutes, respectively, and not significantly different from each other. Both occurred significantly earlier than the tmax associated with slow CRIS (44 +/- 7 min). The Cmax values observed following ivpb (11.2 +/- 1.5 mg/L) and slow CRIS (10.9 +/- 0.9 mg/L) administration were not significantly different from each other, but both were significantly lower than that of fast CRIS (13.4 +/- 1.5 mg/L). The AUCs of slow and fast CRIS were 29.8 +/- 4.8 and 31.2 +/- 3.8 mg/L.h, respectively, and were not significantly different from each other. The AUC of fast CRIS was significantly greater than that observed with ivpb (27.4 +/- 4.3 mg/L.h). No significant difference in ke (fast CRIS 0.32 +/- 0.03 h-1; slow CRIS 0.33 +/- 0.04 h-1; ivpb 0.34 +/- 0.0 h-1) was observed among any of the methods. CONCLUSIONS: CRIS administration of tobramycin resulted in higher AUCs than did ivpb administration. Compared with ivpb, fast CRIS resulted in a higher Cmax, but the tmax values of fast CRIS and ivpb administration were not statistically different. Compared with ivpb, slow CRIS resulted in a more delayed tmax, but the Cmax values of slow CRIS and ivpb were not statistically different.

Treatment of a syngeneic rat tumor with magnetically responsive albumin microspheres labeled with doxorubicin or protein A.

The tumoricidal activity of magnetically responsive albumin microspheres tagged with either doxorubicin or Staphylococcal protein A was tested against an induced mammary adenocarcinoma, 13762, implanted subcutaneously in the tail of female Fischer-344 rats. Magnetically responsive albumin microspheres containing Fe3O4 particles were prepared by an emulsion polymerization method incorporating either doxorubicin or protein A into the albumin matrix. Microspheres were produced with an average diameter of 1 micron (0.2 to 1.5 micron) in a concentration of 10(9) microspheres/mg. Microspheres were injected either directly into the tail artery and localized to the implanted tumor using a permanent bipolar adjustable gap magnet with a field strength of 8000 Oe, or directly into the femoral vein with no magnetic localization. Control groups consisted of animals treated with intravenously or intraarterially administered microspheres containing no active agent, and a no-treatment group. Survival was significantly greater in both the doxorubicin- and protein A-treated animals than in the control groups. First appearance of local metastases was prolonged in only the intraarterial magnetically localized doxorubicin-treated group of animals. Tumor growth rate was significantly depressed in both intraarterially magnetically localized treatment groups when compared to intravenously administered nonlocalized treatment groups. Magnetically responsive albumin microspheres appear to be an effective delivery system for cytotoxic agents and biologic response modifiers. Significant tumoricidal activity can be produced with a one-time administration of these agents utilizing this drug delivery system.