Amphiphilic star-like macromolecules as novel carriers for topical delivery of nonsteroidal anti-inflammatory drugs

The objective of this study was to evaluate amphiphilic star-like macromolecules (ASMs) as a topical drug delivery system. Indomethacin, piroxicam, and ketoprofen were individually encapsulated into the ASMs using coprecipitation. The effects of the ASMs on percutaneous permeation of nonsteroidal anti-inflammatory drugs (NSAIDs) across full thickness, hairless mouse skin were evaluated in vitro using modified Franz diffusion cells. In addition, solubility and in vitro release experiments were performed to characterize ASMs behavior in aqueous media. Poly(ethylene glycol) (PEG) and Pluronic P-85 were used as polymer controls to compare the role of PEG and amphiphilic behavior in the ASMs. In vitro release experiments indicated that ASMs can delay drug release (P⋖05), whereas solubility measurements showed that ASMs can increase NSAIDs aqueous solubility (P⋖05). Percutaneous permeation studies revealed that ASMs decreased both flux and Q₂₄ of drugs compared with the control (P⋖10). Skin pretreatment studies with ASM-containing solution before drug application demonstrated that pretreatment similarly influenced NSAID percutaneous permeation. In conclusion, ASMs likely slow drug permeation through 2 mechanisms, delayed drug diffusion from its core and skin dehydration by its shell. Thus, ASMs may be useful for delayed dermal delivery or prevention of compound permeation through the skin (eg, sunscreens, N,N-diethyl-m-toluamide [DEET]) from aqueous formulations.     

Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01.

PURPOSE: To report mature results of a randomized trial that compared extended-field radiotherapy (EFRT) versus pelvic radiotherapy with concomitant fluorouracil and cisplatin (CTRT) in women with locoregionally advanced carcinomas of the uterine cervix. PATIENTS AND METHODS: Four hundred three women with cervical cancer were randomly assigned to receive either EFRT or CTRT. Patients were eligible if they had stage IIB to IVA disease, stage IB to IIA disease with a tumor diameter > or = 5 cm, or positive pelvic lymph nodes. Patients were stratified by stage and by method of lymph node evaluation. RESULTS: The median follow-up time for 228 surviving patients was 6.6 years. The overall survival rate for patients treated with CTRT was significantly greater than that for patients treated with EFRT (67% v 41% at 8 years; P <.0001). There was an overall reduction in the risk of disease recurrence of 51% (95% CI, 36% to 66%) for patients who received CTRT. Patients with stage IB to IIB disease who received CTRT had better overall and disease-free survival than those treated with EFRT (P <.0001); 116 patients with stage III to IVA disease had better disease-free survival (P =.05) and a trend toward better overall survival (P =.07) if they were randomly assigned to CTRT. The rate of serious late complications of treatment was similar for the two treatment arms. CONCLUSION: Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects.     

Weight cycling did not increase tumor incidence in high fat–fed rats treated with a low-dose 7,12-dimethylbenzyl(1)anthracene

The present study tested the hypothesis that weight cycling (WC, repeated weight gain and loss) increases the tumorigenesis in rats exposed to carcinogen. Female Wistar rats consumed a high-fat diet (35% weight per weight) and were divided: (1) ad lib–fed rats that were treated with 7,12-dimethylbenzyl(1)anthracene (DMBA, 2 mg) at 55 days of age (AL-DMBA); (2) WC rats that were treated with DMBA (WC-DMBA); and (3) vehicle-treated WC rats (WC-VEH). In this study, WC did not alter blood parameter concentrations and did not influence insulin sensitivity. Mammary tissue F₂-isoprostane concentrations were lowest in WC-VEH and highest in AL-DMBA groups. Tumor incidence and burden were similar among all groups. The data obtained from this study do not support our hypothesis. This may be due to low dose of DMBA used, strain and age of the rats, number of WC cycles, and the amount of trans–fatty acids in the diets.     

Genetic, environmental, and gender effects on individual differences in toddler expressive language.

In this article, the authors examined the genetic and environmental factors influencing expressive language development in a sample of 386 toddler twin pairs participating in the Wisconsin Twin Project. Expressive language was assessed using 2 measures from the MacArthur Communicative Development Inventories-Short Form: Total Vocabulary and Two-Word Combination Use (L. Fenson et al., 2000). A sex-limitation structural equation model estimated the contribution of genetics, shared environment, and nonshared environment to individual variation. For vocabulary, heritability was higher for boys than for girls (20% vs. 8%). For word combination use, heritability was higher for girls (28% vs. 10%). However, the majority of individual variation in both boys and girls could be attributed to shared environment (54%-78%).     

The Effect of Area HMO Market Share on Cancer Screening

Objective. Managed care may have widespread impacts on health care delivery for all patients in the areas where they operate. We examine the relationship between area managed care activity and screening for breast, cervical, and prostate cancer among patients enrolled in more managed care plans and patients who are enrolled in less managed plans.
Data and Methods. Data on cancer screening from the 1996 Medical Expenditure Panel Survey (MEPS) were linked to data on health maintenance organization (HMO) and preferred provider organization (PPO) market share and HMO competition at the metropolitan statistical area (MSA) level. Logistic regression analysis was used to examine the relationship between area managed care prevalence and the use of mammography, clinical breast examination, Pap smear, and prostate cancer screening in the past two years, controlling for important covariates.
Results. Among all patients, increases in area-level HMO market share are associated with increases in the appropriate use of mammography, clinical breast exam, and Pap smear (OR for high relative to low managed care areas are 1.75, p <.01, for mammography, 1.58, p <.05, for clinical breast exam, and 1.71, p <.01, for Pap smear). In analyses of subgroups, the relationship is significant only for individuals who are enrolled in the nonmanaged plans; there is no relationship for individuals in more managed plans. No relationship is observed between area HMO market share and prostate cancer screening in any analysis. Neither the level of competition between area HMOs nor area PPO market share is associated with screening rates.
Conclusions. Area-level managed care activity can influence preventive care treatment patterns.     

Impacts of Informal Caregiver Availability on Long-term Care Expenditures in OECD Countries

Objective. To quantify the effects of informal caregiver availability and public funding on formal long-term care (LTC) expenditures in developed countries.
Data Source/Study Setting. Secondary data were acquired for 15 Organization for Economic Cooperation and Development (OECD) countries from 1970 to 2000.
Study Design. Secondary data analysis, applying fixed- and random-effects models to time-series cross-sectional data. Outcome variables are inpatient or home heath LTC expenditures. Key explanatory variables are measures of the availability of informal caregivers, generosity in public funding for formal LTC, and the proportion of the elderly population in the total population.
Data Collection/Extraction Method. Aggregated macro data were obtained from OECD Health Data, United Nations Demographic Yearbooks, and U.S. Census Bureau International Data Base.
Principal Findings. Most of the 15 OECD countries experienced growth in LTC expenditures over the study period. The availability of a spouse caregiver, measured by male-to-female ratio among the elderly, is associated with a $28,840 (1995 U.S. dollars) annual reduction in formal LTC expenditure per additional elderly male. Availability of an adult child caregiver, measured by female labor force participation and full-time/part-time status shift, is associated with a reduction of $310 to $3,830 in LTC expenditures. These impacts on LTC expenditure vary across countries and across time within a country.
Conclusions. The availability of an informal caregiver, particularly a spouse caregiver, is among the most important factors explaining variation in LTC expenditure growth. Long-term care policies should take into account behavioral responses: decreased public funding in LTC may lead working women to leave the labor force to provide more informal care.     

A conceptual framework for evaluating information technologies and decision support systems for bioterrorism preparedness and response.

OBJECTIVES: The authors sought to develop a conceptual framework for evaluating whether existing information technologies and decision support systems (IT/DSSs) would assist the key decisions faced by clinicians and public health officials preparing for and responding to bioterrorism. METHODS: They reviewed reports of natural and bioterrorism related infectious outbreaks, bioterrorism preparedness exercises, and advice from experts to identify the key decisions, tasks, and information needs of clinicians and public health officials during a bioterrorism response. The authors used task decomposition to identify the subtasks and data requirements of IT/DSSs designed to facilitate a bioterrorism response. They used the results of the task decomposition to develop evaluation criteria for IT/DSSs for bioterrorism preparedness. They then applied these evaluation criteria to 341 reports of 217 existing IT/DSSs that could be used to support a bioterrorism response. Main Results: In response to bioterrorism, clinicians must make decisions in 4 critical domains (diagnosis, management, prevention, and reporting to public health), and public health officials must make decisions in 4 other domains (interpretation of bioterrorism surveillance data, outbreak investigation, outbreak control, and communication). The time horizons and utility functions for these decisions differ. From the task decomposition, the authors identified critical subtasks for each of the 8 decisions. For example, interpretation of diagnostic tests is an important subtask of diagnostic decision making that requires an understanding of the tests' sensitivity and specificity. Therefore, an evaluation criterion applied to reports of diagnostic IT/DSSs for bioterrorism asked whether the reports described the systems' sensitivity and specificity. Of the 217 existing IT/DSSs that could be used to respond to bioterrorism, 79 studies evaluated 58 systems for at least 1 performance metric. CONCLUSIONS: The authors identified 8 key decisions that clinicians and public health officials must make in response to bioterrorism. When applying the evaluation system to 217 currently available IT/DSSs that could potentially support the decisions of clinicians and public health officials, the authors found that the literature provides little information about the accuracy of these systems.     

Can we identify the poorest quality of life? Assessing the importance of quality of life using the WHOQOL-100

In this study, WHOQOL survey data obtained from 4802 sick and well participants in 15 countries were used to investigate the relationship between judgements about different dimensions of quality of life (QOL) (core scores) and the importance attributed to them. As a theoretical framework, we applied the WHOQOL Group's (1995) definition of QOL which indicates that those who report the very poorest QOL will be least likely to have met their own '...goals, expectations, standards and concerns'. Those with the poorest QOL would therefore be expected to show the biggest difference between core and importance scores, and therefore be distinguishable from respondents whose QOL was poor, better or best. The main effects from overall analyses confirmed that those reporting the largest negative differences tended to report the poorest QOL and also attached a high degree of importance to these dimensions. Evidence for a decreasing differential across the four groups (poorest to best) was confirmed for the majority (18) of facets. However facet level analyses comparing groups with different levels of QOL showed that only five facets distinguished those with the poorest QOL from those whose QOL was poor, so the theory is not well supported. Furthermore the contribution of core-importance facet differences reduced the overall prediction of QOL, when compared with a regression of core scores alone. Importance information about specific facets may have limited potential to be used alongside the main instrument to identify areas of the poorest QOL for clinical or social action.