Permethrin-resistant human head lice,Pediculus capitis,and their treatment

OBJECTIVE: To compare the pediculicidal activity of Ovide lotion and its active ingredient, 0.5% malathion, with Nix and its active ingredient, 1% permethrin, in permethrin-resistant head lice. DESIGN: In vitro pediculicidal product and active ingredient comparison. The presence of knockdown resistance-type mutations (T929I and L932F) was validated by DNA sequencing. SETTING: University of Massachusetts-Amherst; University of Miami School of Medicine, Miami, Fla; Plantation and Homestead, Fla; and Mathis, Tex.Other PARTICIPANTS: Lice were collected in 3 geographical regions within the United States and in Yamburara, Ecuador, from healthy but infested individuals.Intervention Within 3 to 6 hours of collection, lice were given a blood meal, exposed to products or active ingredients, and observed at regular intervals. MAIN OUTCOME MEASURES: Percent mortality of lice at regular intervals after exposure to products or active ingredients and presence of T929I and L932F mutations. RESULTS: South Florida lice exhibited a significantly slower mortality response to permethrin compared with susceptible Ecuadorian lice. Ovide and malathion killed permethrin-resistant lice faster than Nix or permethrin. The presence of T929I and L932F in permethrin-resistant south Florida lice was confirmed by DNA sequencing. The population of Texas lice from Mathis was slightly resistant to permethrin and included 13% with resistant genotypes. CONCLUSIONS: The presence of the T929I and L932F mutations was confirmed by DNA sequencing in lice collected from children in south Florida that were resistant to the pediculicidal effects of permethrin and the leading permethrin-based head lice product, Nix. Malathion resistance was not observed in this study. The data also show that Ovide killed these same permethrin-resistant head lice approximately 10 times faster than permethrin or Nix.     

Assessing mammographers' accuracy. A comparison of clinical and test performance

Direct estimation of mammographers' clinical accuracy requires the ability to capture screening assessments and correctly identify which screened women have breast cancer. This clinical information is often unavailable and when it is available its observational nature can cause analytic problems. Problems with clinical data have led some researchers to evaluate mammographers using a single set of films. Research based on these test film sets implicitly assumes a correspondence between mammographers' accuracy in the test setting and their accuracy in a clinical setting. However, there is no evidence supporting this basic assumption. In this article we use hierarchical models and data from 27 mammographers to directly compare accuracy estimated from clinical practice data to accuracy estimated from a test film set. We found moderate positive correlation [ rho; = 0.206 with 95% credible interval (-0.142-0. 488)] between mammographers' overall preponderance to call a mammogram positive. However, we found no evidence of correlation between clinical and test accuracy [ rho; = -0.025 with 95% credible interval (-0.484-0.447)]. This study is limited by the relatively small number of mammographers evaluated, by the somewhat restricted range of observed sensitivities and specificities, and by differences in the types of films evaluated in test and clinical datasets. Nonetheless, these findings raise important questions about how mammographer accuracy should be measured.     

A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel

BACKGROUND: Prostate cancer is the second leading cause of cancer mortality among men in the U.S. To the authors' knowledge, there is no proven, effective, second-line therapy for docetaxel-refractory disease. Recent data suggest that platinum salts may be effective when combined with taxanes in metastatic hormone-refractory prostate cancer (HRPC). The authors conducted a phase 2 trial of docetaxel plus carboplatin chemotherapy in this disease setting. METHODS: Eligible men had metastatic HRPC that had progressed during or within 45 days after the completion of docetaxel-based chemotherapy. Patients were treated with intravenous docetaxel at a dose of 60 mg/m(2) plus carboplatin at an area under the curve of 4 once every 21 days until they had either disease progression or unacceptable toxicity. RESULTS: Thirty-four patients were enrolled. Therapy was tolerated reasonably well; Grade 3 leukopenia (graded according to the Common Toxicity Criteria grading system) was the most common adverse event (experienced by 56% of patients), but there was only 1 episode of febrile neutropenia reported. Prostate-specific antigen (PSA) declines > or =50% were noted in 18% of patients, and measurable responses were observed in 14%. The median duration of PSA response was 5.7 months. The median progression-free survival was 3 months, and the median overall survival was 12.4 months. Patients were more likely to respond to the combination if they previously had responded to docetaxel. CONCLUSIONS: In men with HRPC who developed progressive disease during or shortly after treatment with docetaxel, the addition of carboplatin resulted in modest additional activity. Taxane-refractory HRPC is an area of unmet need, and the current trial has provided evidence that platinum chemotherapy may be an important therapeutic option.     

Dissociable neural mechanisms for determining the perceived heaviness of objects and the predicted weight of objects during lifting: an fMRI investigation of the size-weight illusion

In size-weight (SW) illusions, people learn to scale their fingertip forces for lifting small and big objects of equal weight even though they fail to learn perceptually that both objects have the same weight. The question then arises as to what the separate neural mechanisms are for determining the perceived heaviness of objects and the predicted weight of these objects during lifting. To answer this question, we used fMRI to first identify areas that code for the size, weight, and density of objects using an adaptation paradigm. We then contrasted BOLD in the SW illusion condition in which subjects falsely perceived the smaller of two equally weighted objects as heavier versus a condition in which size and weight did not differ between objects. Sensory areas in the parietal and temporal cortex adapted to the size of objects and the primary motor area (M1) contralateral to the lifting hand adapted to the weight of objects. The ventral premotor area (PMv), which did not adapt to either the size or the weight of objects, adapted instead to the density of objects, and responded more when subjects falsely perceived differences in weight between objects in the SW illusion condition. Taken together, we conclude that the real-world properties of objects, such as size and weight, are computed by sensory areas and by M1 respectively, whereas the perceived heaviness of objects, presumably based on their apparent density, is computed by PMv, a higher-order area well placed to integrate sensory information about the size of objects and the weight of objects.     

Phase II study of docetaxel, estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: a final report of CALGB 9780. Cancer and Leukemia Group B.

PURPOSE: To investigate the combination of docetaxel, estramustine (EM), and low-dose hydrocortisone in men with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Combinations of EM with other antimitotic agents such as docetaxel are synergistic in vitro and show significant clinical activity in patients with HRPC. We studied intravenous administration of docetaxel 70 mg/m(2), oral estramustine, and low-dose daily hydrocortisone in men with HRPC who demonstrated progression after initial hormone therapy. RESULTS: Of the 47 men enrolled onto this multicenter cooperative group study, 46 were assessable for response and/or toxicity. In the 24 patients with measurable disease, there were three complete and nine partial responses for a measurable disease response rate of 50% (12 of 24 patients; 95% confidence interval [CI], 27% to 73%). In the 44 patients in whom pretreatment prostate-specific antigen (PSA) was elevated, 30 (68%) had a 50% or greater decrease, and 25 (57%) had a 75% or greater decrease in PSA. The combined measurable disease and biochemical response rate in all 46 assessable patients was 54% (three complete responses, 22 partial responses, 95% CI, 37% to 71%). The predominant toxicity was neutropenia, with 26% of patients having grade 3 and 30% having grade 4 granulocytopenia; there were no episodes of febrile neutropenia. Other common but mild adverse effects included malaise/fatigue, peripheral edema, and hyperglycemia. The incidence of thromboembolic events during therapy was 9%. With a median follow-up of 17 months, the median survival was 20 months. The median time to disease progression was 8 months for all patients, and 10 months for those with measurable disease. CONCLUSION: This therapy is efficacious and moderately well tolerated in HRPC and should be compared in a phase III trial with mitoxantrone and prednisone.     

Cost-justification analysis of prenatal maternal serum alpha-feto protein screening

The costs to an insurer of a 10-year maternal serum alpha-feto protein (MSAFP) screening program were subtracted from future medical care costs avoided by the insurer (benefits) to examine whether such a program would be cost-justified from the perspective of a managed health care system (i.e., result in net costs greater than or equal to 0). The analysis considered MSAFP screening for neural tube defects (NTDs) alone and then was repeated to consider screening for both NTDs and Down's syndrome. Using a 5% discount rate for future dollars, the costs to the insurer of a screening program for NTDs alone over 10 years exceeded costs avoided by $10.00 per person screened. Adding screening for Down's syndrome using the same MSAFP test increased the net cost by $22.00 to a total of--$32.00 per screenee. The estimate of the cost to the insurer was sensitive to assumptions regarding the costs of medical care avoided, the expense of MSAFP, the proportion of screened women requiring a genetic amniocentesis, and the cost of that procedure. The conclusion that screening would not result in a cost savings to the insurer was not changed by reasonable assumptions regarding 1) the appropriate discount rate; 2) the costs of MSAFP; 3) the costs of genetic amniocentesis; 4) the sensitivity of MSAFP; 5) the proportion of the population requiring genetic amniocentesis; and 6) the costs of 10 years of medical care for someone affected by Down's syndrome or an NTD. Other analyses suggested that screening for NTDs or Down's syndrome would be cost-justified when viewed from the perspective of society. The present work suggests this conclusion does not hold when the perspective of the insurer is taken because avoided costs of care realized by society exceed those realized by the insurer.