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Background: Although tuberculous uveitis remains a major cause of ocular morbidity in the developing world, there is no consensus on which diagnostic test or testing strategy is the most cost effective. In this study we carried out a cost-effectiveness analysis to determine the most cost-effective diagnostic test strategy., Methods: In this prospective study, we recruited 102 patients from Singapore National Eye Centre with signs suggestive of tuberculous uveitis. Using prospective data from this cohort and from published meta-analyses, we modelled the incremental cost effectiveness of the following strategies: tuberculin skin test (TST) only; interferon-γ release assay (IGRA) only; IGRA following a positive TST result; and dual-test strategy, conducting TST and IGRA at presentation. Incremental cost-effectiveness ratios (ICERs) were calculated for each strategy and analysed using a willingness-to-pay threshold of $50,000 per quality-adjusted life year (QALY) gained., Results: In our population, the least cost effective was the IGRA-only strategy. The dual-test strategy was the most cost effective, with an improvement of 0.017 QALY at an incremental cost of $190 relative to the TST-only strategy (ICER $11,500); while the TST-only strategy was more cost effective than the third strategy, using IGRA following a positive TST result (ICER $3610). This remained consistent while varying the costs of IGRA and TST, the incidence of tuberculosis and tuberculous uveitis, as well as the diagnostic accuracy of IGRA and TST found in previous studies in various populations., Conclusions: The dual-test strategy (performing TST and IGRA at presentation) was the most cost effective strategy for the diagnosis of tuberculous uveitis in our population., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Foreign body ingestion or insertion is occasionally encountered by radiologists and is associated with significant morbidity, financial burden, and potential mortality. Incarcerated individuals are a unique group where foreign body ingestion or insertion is more common than the general population. Motivations include reprieve from the confines of prison, sexual stimulation or victimization, or may be secondary to compulsions in patients with psychiatric disorders. These foreign bodies may lead to perforation, obstruction, or infection. Radiologists can help clinicians identify unexpected ingested or inserted objects as well as the sequelae of foreign body ingestion or insertion., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: There is consensus that development and evaluation of a systems-oriented approach for child obesity prevention and treatment that includes both primary and secondary prevention efforts is needed. This article describes the study design and baseline data from the Texas Childhood Obesity Research Demonstration (TX CORD) project, which addresses child obesity among low-income, ethnically diverse overweight and obese children, ages 2-12 years; a two-tiered systems-oriented approach is hypothesized to reduce BMI z-scores, compared to primary prevention alone., Methods: Our study aims are to: (1) implement and evaluate a primary obesity prevention program; (2) implement and evaluate efficacy of a 12-month family-centered secondary obesity prevention program embedded within primary prevention; and (3) quantify the incremental cost-effectiveness of the secondary prevention program. Baseline demographic and behavioral data for the primary prevention community areas are presented., Results: Baseline data from preschool centers, elementary schools, and clinics indicate that most demographic variables are similar between intervention and comparison communities. Most families are low income (≤$25,000) and Hispanic/Latino (73.3-83.8%). The majority of parents were born outside of the United States. Child obesity rates exceed national values, ranging from 19.0% in preschool to 35.2% in fifth-grade children. Most parents report that their children consume sugary beverages, have a television in the bedroom, and do not consume adequate amounts of fruits and vegetables., Conclusions: Interventions to address childhood obesity are warranted in low-income, ethnically diverse communities. Integrating primary and secondary approaches is anticipated to provide sufficient exposure that will lead to significant decreases in childhood obesity.

Background: Residents need to acquire an understanding of the biopsychosocial aspects of caring for older adults with chronic illness, along with effective use of interdisciplinary services inside and outside of the hospital., Objective: We expanded the geriatric medicine experience for second-year internal medicine residents and present the results of the first year's experience., Methods: We paired a mandatory rotation for postgraduate year-2 internal medicine residents (2 weeks of day and 1 week of night inpatient experience in the Acute Care for Elders Unit), and a 1-week outpatient systems-based practice experience with online modules and readings. Evaluation included a case presentation, an oral examination, a written questionnaire for all residents, and a global assessment of the residents' performance on the geriatrics portion of the 2012 In-Training Examination (ITE)., Results: All residents passed their oral examination; there was little difference between classes in systems-based practice knowledge. More than 90% (21 of 23) of the residents who took the rotation reported that it left a lasting impression on how they would care for their patients. Mean ITE scores in geriatrics for all residents increased from 53% (versus 61% overall) in 2010 to 87% (versus 81%) in 2012, although they dropped to 69% (versus 82%) in 2013., Conclusions: A rotation in geriatrics that is highly rated and covers both acute care and systems-based practice concepts is feasible for internal medicine residents. Residents did not learn detailed knowledge about specific programs for older adults, but clinical geriatrics knowledge improved.

Objective: Food reinforcement and delay discounting (DD) independently predict body mass index (BMI), but there is no research studying whether these variables interact to improve prediction of BMI., Methods: BMI, the relative reinforcing value of high (PMAXHED ) and low (PMAXLED ) energy dense food, and DD for $10 and $100 future rewards (DD10 , DD100 ) were measured in 199 adult females., Results: PMAXHED (P = 0.017), DD10 (P = 0.003), and DD100 (P = 0.003) were independent predictors of BMI. The interaction of PMAXLED × DD10 (P = 0.033) and DD100 (P = 0.039), and PMAXHED × DD10 (P = 0.038) and DD100 (P = 0.045) increased the variance accounted for predicting BMI beyond the base model controlling for age, education, minority status, disinhibition, and dietary restraint. Based on the regression model, BMI differed by about 2 BMI units for low versus high food reinforcement, by about 3 BMI units for low versus high DD, and by about 4 BMI units for those high in PMAXHED , but low in DD versus high in PMAXHED and high in DD., Conclusion: Reducing DD may help prevent obesity and improve treatment of obesity in those who are high in food reinforcement., (Copyright © 2013 The Obesity Society.)

Background: Obesity runs in families, and family-based behavioral treatment (FBT) is associated with weight loss in overweight/obese children and their overweight/obese parents. This study was designed to estimate the costs and cost-effectiveness of FBT compared to separate group treatments of the overweight/obese parent and child (PC)., Methods: Fifty overweight/obese 8- to 12-year-old children with overweight/obese parents were randomly assigned to 12 months of either FBT or PC treatment program. Assessment of societal costs (payer plus opportunity costs) were completed based on two assumptions: (1) programs for parent and child were available on separate days (PC-1) or (2) interventions for parent and child were available in the same location at sequential times on the same day (PC-2). Cost-effectiveness was calculated based on societal cost per unit of change using percent overBMI for children and weight for parents., Results: The average societal cost per family was $1,448 for FBT and $2,260 for PC-1 (p < 0.001) and $2,124 for PC-2 (p < 0.001). Child cost-effectiveness for FBT was $209.17/percent overBMI, compared to $1,036.50/percent overBMI for PC-1 and $973.98/percent overBMI for PC-2. Parent cost-effectiveness was $132.97/pound (lb) for FBT and $373.53/lb (PC-1) or $351.00/lb (PC-2)., Conclusions: For families with overweight/obese children and parents, FBT presents a lower cost per unit of weight loss for parents and children than treating the parent and child separately. Given the high rates of pediatric and adult obesity, FBT may provide a unique cost-effective platform for obesity intervention that alters weight in overweight/obese parents and their overweight/obese children.

Purpose: To estimate the economic cost of myopia among adults aged 40 years and older in Singapore., Methods: A substudy of 113 Singaporean adults aged 40 years and older with myopia (spherical equivalent refraction of at least -0.5 diopters) in the population-based ancillary study of Singapore Chinese Eye Study (SCES) was conducted. A health expenditure questionnaire was used to assess the direct cost of myopia., Results: A total of 113 (90.4%) of 125 myopic subjects participated in the survey. The mean cost was approximately SGD$900 (USD$709) per person per year. The lifetime per capita cost ranged from SGD$295 (USD$232) for those with 0 year's duration to SGD$21,616 (USD$17,020) for those with 80 years' duration. Costs of spectacles, contact lenses, and optometry services were the major cost drivers, contributing to an average of 65% of total costs. Seven subjects (6.2%) had undergone LASIK surgery, resulting in a cost of SGD$4891 (USD$3851) per patient per year. Three subjects (2.7%) reported annual costs of (SGD$33 or USD$26) for complications due to LASIK surgery or contact lenses. There was an increasing cost of myopia in adults who started to wear glasses at earlier ages. By applying our cost data to age-specific myopia prevalence data in the whole population in the country, the total cost was estimated to be approximately SGD$959 (USD$755) million per year in Singapore., Conclusions: Myopia is associated with substantial out-of-pocket expenditure, imposing considerable economic burden for patients. Myopia is a disorder with immense societal costs and public health impact.

Purpose: Depression is a common problem among people with visual impairment and contributes to functional decline. This article presents a study protocol to evaluate a new model of care for those patients with depressive symptoms in which psychological treatment is integrated into low vision rehabilitation services. Low vision staff will be trained to deliver "problem solving therapy for primary care" (PST-PC), an effective psychological treatment developed specifically for delivery by non-mental health care staff. PST-PC is delivered in 8 weekly telephone sessions of 30-45 minutes duration and 4 monthly maintenance sessions. We predict this new integrated model of care will significantly reduce depressive symptoms and improve the quality of life for people with visual impairment., Methods and Design: A randomized controlled trial of PST-PC will be implemented nationally across low vision rehabilitation services provided by Vision Australia. Clients who screen positive for depressive symptoms and meet study criteria will be randomized to receive PST-PC or usual care, consisting of a referral to their general practitioner for more detailed assessment and treatment. Outcome measures include depressive symptoms and behaviors, quality of life, coping and psychological adjustment to visual impairment. Masked assessments will take place pre- and post-intervention as well as at 6- and 12-month follow-up., Conclusion: We anticipate that this innovative service delivery model will lead to sustained improvements in clients' quality of life in a cost effective manner and provide an innovative service delivery model suitable for other health care areas in which depression is co-morbid.

Introduction: Myopia is a significant public health problem in Singapore with estimates that more than 50% of the population is affected by it by the time of adulthood. Childhood obesity is also increasing and has been linked to long-term health problems. Recent studies have found that Singaporean children in Primary 1 spend less than 3 hours a day outdoors which is less than children in other countries. Physical activity has been shown to be protective against obesity and recently, there has been some evidence to suggest that time spent outdoors may reduce the prevalence and severity of myopia. This study aims to explore the barriers and enablers to children in Singapore participating in outdoor activities., Materials and Methods: Qualitative data, gathered from focus group discussions was thematically analysed against the PRECEDE component of the PRECEDE-PROCEED model which provided a conceptual framework for examining factors relevant to children participating in an outdoor activity intervention. A total of 31 people participated in 4 focus groups held over a 6-month period., Results: This feasibility study was exploratory in nature but provided valuable information concerning barriers and enablers to participation. Data informed the development of a larger study., Conclusion: Results indicated that families preferred structured activities such as orienteering and a choice of weekend attendance days and times.

Aim: Genetic factors have been found to affect warfarin maintenance dose and a key factor for the successful clinical implementation of warfarin pharmacogenetic testing (WPGT) is economic sustainability. We aimed to estimate the willingness-to-pay (WTP) and preferences for WPGT in Singaporean Chinese subjects. Methods & subjects: A total of 197 warfarin patients and 187 members of the public completed a questionnaire. The discrete choice methodology was used and the choice model was estimated using hierarchical Bayes. Marginal WTP, attribute importance and WTP for three hypothetical WPGTs were calculated from the estimated utilities., Results: Both patients and the public placed most emphasis on side effects, followed by cost, number of International Normalized Ratio tests and 'nature of test'. WTP for WPGT ranged from S$160 to S$730., Conclusion: WPGTs are likely to be economically sustainable.

Purpose: Selective endothelial transplantation in the form of Descemet's stripping endothelial keratoplasty (DSEK) is rapidly replacing traditional full-thickness penetrating keratoplasty (PK) for endothelial disease. An incremental cost-effectiveness analysis was performed to determine whether the benefits of DSEK are worth the additional costs., Design: Retrospective cohort study., Participants: Patients at the Singapore National Eye Center, a tertiary eye center in Singapore, with Fuchs' dystrophy or bullous keratopathy who underwent either PK or DSEK., Intervention: Patients underwent either PK (n = 171) or DSEK (n = 93) from January 2001 through December 2007. Data were collected from inpatient and outpatient notes corresponding to the time immediately before the procedure to up to 3 years after., Main Outcome Measures: Improvements in best spectacle-corrected visual acuity were used to calculate the increase in quality-adjusted life years (QALYs) 3 years after the procedure. This was combined with hospital charges (a proxy for costs) to determine incremental cost-effectiveness ratios (ICERs) comparing PK with no intervention and DSEK with PK., Results: Three-year charges for DSEK and PK were $7476 and $7236, respectively. The regression-adjusted improvement in visual acuity for PK relative to no intervention was -0.613 logarithm of the minimum angle of resolution (logMAR) units (P<0.001), and for DSEK relative to PK, it was -0.199 logMAR units (P = 0.045). The regression-adjusted marginal gain in utility for PK relative to no intervention was 0.128 QALYs (P<0.001) and for DSEK relative to PK was 0.046 QALYs (P = 0.031). This resulted in ICERs of $56 409 per QALY for PK relative to no intervention and $5209 per QALY for the more expensive DSEK relative to PK., Conclusions: If the goal is to maximize societal health gains given fixed resources, DSEK should be the preferred strategy. For a fixed budget, it is possible to achieve greater QALY gains by providing DSEK to as many patients as possible (and nothing to others), rather than providing PK., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: Interventions that mitigate drowning risk in developing countries are needed. This study presents the cost-effectiveness of a low-cost, scalable injury and drowning prevention program called Prevention of Child Injuries through Social-Intervention and Education (PRECISE) in Bangladesh., Methods: Between 2006 and 2010, the 2 components of PRECISE (Anchal, which sequestered children in crèches [n = 18 596 participants], and SwimSafe, which taught children how to swim [n = 79421 participants]) were implemented in rural Bangladesh. Mortality rates for participants were compared against a matched sample of nonparticipants in a retrospective cohort analysis. Effectiveness was calculated via Cox proportional hazard analysis. Cost-effectiveness was estimated according to World Health Organization-CHOosing Interventions that are Cost Effective guidelines., Results: Anchal costs between $50.74 and $60.50 per child per year. SwimSafe costs $13.46 per child. For Anchal participants, the relative risk of a drowning death was 0.181 (P = .004). The relative risk of all-cause mortality was 0.56 (P = .001). For SwimSafe, the relative risk of a drowning death was 0.072 (P < .0001). The relative risk of all-cause mortality was 0.750 (P = .024). For Anchal, the cost per disability-adjusted life-year (DALY) averted is $812 (95% confidence interval: $589\x{2013}$1777). For SwimSafe, the cost per DALY averted is $85 ($51\x{2013}$561). Combined, the cost per DALY averted is $362 ($232\x{2013}$1364)., Conclusions: Based on World Health Organization criteria, PRECISE is very cost-effective and should be considered for implementation in other areas where drowning is a significant problem.

Background: Based on national estimates, the majority of working adults are overweight or obese. Overweight and obesity are associated with diminished health, productivity, and increased medical costs for employers. Worksite-based weight loss interventions are desirable from both employee and employer perspectives., Purpose: To investigate organizational- and employee-level participation in a group-randomized controlled worksite-based weight loss trial., Methods: Using a set of inclusion criteria and pre-established procedures, we recruited worksites (and overweight/obese employees from enrolled worksites) from the North Carolina Community College System to participate in a weight loss study. Recruitment results at the worksite (organization) and employee levels are described, along with an assessment of representativeness., Results: Eighty-one percent (48/59) of community colleges indicated initial interest in participating in the weight loss study, and of those, 17 colleges were enrolled. Few characteristics distinguished enrolled community colleges from unenrolled colleges in the overall system. Eligible employees (n = 1004) at participating colleges were enrolled in the weight loss study. On average, participants were aged 46.9 years (SD = 12.1 years), had a body mass index (BMI) of 33.6 kg/m(2) (SD = 7.9 kg/m(2)), 83.2% were White, 13.3% African American, 82.2% female, and 41.8% reported holding an advanced degree (master's or doctoral degree). Compared with the larger North Carolina Community College employee population, participants most often were women, but few other differences were observed., Limitations: Employees with reduced computer access may have been less likely to participate, and limited data on unenrolled individuals or colleges were available., Conclusions: Community colleges are willing partners for weight loss intervention studies, and overweight/obese employees were receptive to joining a weight loss study offered in the workplace. The results from this study are useful for planning future worksite-based weight loss interventions and research studies that achieve high participation rates at the employee and organizational levels.

One way in which to modify food purchases is to change prices through tax policy, subsidy policy, or both. We reviewed the growing body of experimental research conducted in the laboratory and in the field that investigates the following: the extent to which price changes influence purchases of targeted and nontargeted foods, total energy, or macronutrients purchased; the interaction of price changes with adjunctive interventions; and moderators of sensitivity to price changes. After a brief overview of economic principles and observational research that addresses these issues, we present a targeted review of experimental research. Experimental research suggests that price changes modify purchases of targeted foods, but research on the overall nutritional quality of purchases is mixed because of substitution effects. There is mixed support for combining price changes with adjunctive interventions, and there are no replicated findings on moderators to price sensitivity in experiments. Additional focused research is needed to better inform food policy development with the aim of improving eating behavior and preventing obesity.

Purpose: It is known that a person's socioeconomic status (SES; individual-level SES) is closely correlated with his or her degree of visual impairment. Whether there is an independent relationship between area-level measures of SES (e.g., living in a lower SES environment) and visual impairment is unclear. This study describes the associations of area-level SES with visual impairment., Methods: The authors conducted two population-based cross-sectional studies of 3280 adult Malays and 3400 adult Indians living in Singapore. Visual impairment was defined as LogMAR visual acuity >0.30 in the better-seeing eye. Area-level SES measures (e.g., proportion of people not speaking English, proportion of people with low income) were derived from the Singapore's 2000 population census., Results: Increasing age and individual-level SES measures (including lower education level, lower income level, and lower occupational status) were significantly associated with increased odds of visual impairment. In analyses adjusting for age and individual-level SES measures, many area-level SES measures (e.g., higher proportion of people not using English, higher proportion of people with low income) were also significantly associated with increased odds of visual impairment. These associations were consistently observed in both Malays and Indians., Conclusions: These data suggest that not only is a person's SES, but the SES of his or her immediate community, is associated with visual impairment. Further research is needed to investigate the underlying causes of visual health disparities and to improve the eye health of communities with lower SES.

Purpose: This study sought to determine the cost effectiveness of deep anterior lamellar keratoplasty (DALK) compared with penetrating keratoplasty (PK) for the treatment of keratoconus. DALK is associated with lower rates of postoperative complications compared with PK, but is a more expensive procedure; whether it is cost effective compared with PK is unknown., Design: The study was an incremental cost-utility analysis from a health systems perspective using retrospective data on a cohort of patients with severe keratoconus., Methods: The analysis was conducted using 1-year cost and outcomes data from 148 keratoconus patients, representing 102 PK and 46 DALK cases, seen for corneal grafts between January 1991 and January 2009 at the Singapore National Eye Center. The main outcome assessed was the incremental cost-utility ratios associated with PK and DALK for the treatment of keratoconus., Results: Over a 20-year period, PK was the lower cost procedure and had an incremental cost-utility ratio of $3,750 per quality-adjusted life-year compared with no surgical treatment. Compared with PK, DALK has an incremental quality-adjusted life-year gain of 0.8 and an incremental cost of $2,420, for an incremental cost-utility ratio of $3,025 per quality-adjusted life-year., Conclusions: Compared with PK, DALK has a favorable cost-effectiveness ratio and, resources permitting, should be considered as a first-line treatment for keratoconus. Additional studies are needed to confirm the expected advantages of DALK over PK when it comes to long-term graft failure rates., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To estimate the prevalence and costs of respiratory illness for workers in coal mining, compared with other US industries., Methods: Using 5 years of insurance claims data for an annual average of 96,240 adult males, we model the probability and costs of respiratory illness as a function of workers' industry and other factors., Results: Controlling for nonindustry factors, workers in coal mining had significantly higher rates of respiratory illness claims (by 2.1% to 3.3% points) compared with other mining, agriculture, construction, and manufacturing. For coal mining workers with respiratory illness, annual medical care costs for these claims were also significantly higher (by $111 to $289). Surprisingly, drug costs were mostly lower (by $17 to $268)., Conclusions: Our findings underscore the continued importance and potential cost effectiveness of measures to protect miners from harmful occupational exposures, particularly to coal dust.

There is limited research on how taxes and subsidies would influence the energy and nutritional quality of food purchases. Using an experimental analogue purchasing task, we examined the effects of increasing the price of high-calorie-for-nutrient foods or reducing the price of low-calorie-for-nutrient foods by 12.5% and 25% on mothers' purchases of 68 common foods and drinks. Taxing less healthy foods with low nutrient density reduced energy (caloric) intake, while reducing the proportion of fat and increasing the proportion of protein purchased. Subsidizing more healthful foods with high nutrient density increased energy intake, without changing the macronutrient profile of foods purchased. These results favor taxes as a way to reduce caloric intake.

The purpose of this study was to evaluate the oral absorption characteristics of a phospholipid-drug conjugate, comprising direct conjugation between the lecithin and the drug moiety through the sn-2 position. We investigated the mechanisms involved with the trafficking of this conjugate following oral administration in the gastrointestinal (GI) lumen, within the enterocyte and further. A phospholipid-valproic acid conjugate (DP-VPA) was utilized as a model molecule. The oral absorption of this conjugate in rats was investigated following administration in long (LCT) vs. medium (MCT) chain triglyceride formulations, and in the postprandial vs. fasted state. Oral administration within the LCT solution caused more than a 3-fold increase in DP-VPA bioavailability in comparison to the MCT solution. Moreover, a significant food effect was evident for DP-VPA. Hence, we evaluated the lymphatic transport of DP-VPA in mesenteric lymph duct cannulated freely moving rats. Sixty percent of the absorbed DP-VPA was associated with lymphatic transport. Similar DP-VPA absorption was obtained in secretory type II PLA(2) knockout mice (C57BL/6) and in control mice (BALB/c). Moreover, nil DP-VPA degradation in serum and very low (4.8%) degradation by bee venom PLA(2)in vitro were obtained. In conclusion, direct conjugation between the drug and the phospholipid produces a complex having unique absorption properties that include: (1) a stable complex that does not undergo degradation in the GI tract; (2) permeation through the gut wall and entering intact to the enterocyte; and (3) association with chylomicron in the enterocyte and reaching the systemic circulation via the lymphatic route. These unique properties may be of interest in drug delivery.

Objective: To quantify the increase in the likelihood of a fall injury and medical costs of treating fall injuries among elderly individuals with select mental health (MH), substance abuse (SA), and cognitive disorders compared with the general elderly population., Methods: The authors used a random sample (N = 601,922) of claimants in the 2001 Medicare fee-for-service 5% Standard Analytic File. Using logistic regressions, the authors estimated the odds of sustaining a medically attended fall injury as a function of each MH, cognitive, and SA condition and select demographic characteristics. The authors also used an ordinary least squares regression model to compare the increase in costs associated with fall injuries for those with MH/SA conditions compared to those without MH/SA conditions., Results: The odds of a fall injury are between 1.5 and 4.5 times greater for those with MH and SA conditions among both elderly men and women. Odds of a fall injury among elderly individuals with Alzheimer disease and other dementias are at least three times greater, and the differential increases with age. The increases in cost resulting from a fall injury are greater among both elderly men and women with MH conditions and Alzheimer disease and other dementias and among elderly women with SA conditions., Conclusion: The substantial burden of fall injuries among the elderly with MH/SA conditions suggests the need to direct fall prevention and mitigation strategies specifically toward this vulnerable population.

Genetic or pharmacological alteration of the activity of the histone deacetylase 6 (HDAC6) induces a parallel alteration in cell migration. Using tubacin to block deacetylation of alpha-tubulin, and not other HDAC6 substrates, yielded a motility reduction equivalent to agents that block all NAD-independent HDACs. Accordingly, we investigated how the failure to deacetylate tubulin contributes to decreased motility in HDAC6-inhibited cells. Testing the hypothesis that motility is reduced because cellular adhesion is altered, we found that inhibiting HDAC6 activity towards tubulin rapidly increased total adhesion area. Next, we investigated the mechanism of the adhesion area increase. Formation of adhesions proceeded normally and cell spreading was more rapid in the absence of active HDAC6; however, photobleaching assays and adhesion breakdown showed that adhesion turnover was slower. To test the role of hyperacetylated tubulin in altering adhesion turnover, we measured microtubule dynamics in HDAC6-inhibited cells because dynamic microtubules are required to target adhesions for turnover. HDAC6 inhibition yielded a decrease in microtubule dynamics that was sufficient to decrease focal adhesion turnover. Thus, our results suggest a scenario in which the decreased dynamics of hyperacetylated microtubules in HDAC6-inhibited cells compromises their capacity to mediate the focal adhesion dynamics required for rapid cell migration.

Purpose: To quantify annual costs attributable to obesity, including both increased medical expenditures and absenteeism, separately for overweight and three categories of obesity (i.e., obesity grades I, II, and III) among men and women with full-time employment., Design: Standard econometric methods were used to separately estimate overweight and obesity-attributable medical expenditures and absenteeism., Setting: The civilian noninstitutionalized population of the United States., Sample: Two nationally representative and publicly available datasets (with response rates of at least 60%) were restricted to participants 18 to 64 years old and employed full-time for the entire year. The final datasets used to estimate obesity-attributable medical expenditures and absenteeism included 20,329 and 25,427 adults, respectively. MEASURES. Annual medical expenditures and missed work days due to illness or injury. ANALYSIS RESULTS: Overweight and obesity-attributable costs range from dollar 175 per year for overweight male employees to dollar 2485 per year for grade-II obese female employees. The costs of obesity (excluding overweight) at a firm with 1000 employees are estimated to be dollar 285,000 per year, Conclusions: Obesity results in significant increases in medical expenditures and absenteeism among full-time employees. Approximately 30% of the total costs result from increased absenteeism, and although those with grade-III obesity represent only 3% of the employed population, they account for 21% of the costs due to obesity. These estimates do not consider other potential costs associated with obesity, including disability and presenteeism.

The increased prevalence and costs associated with the obesity epidemic have made preventive efforts a public health priority. Public health has historically relied on a series of targeted regulations, taxes, and education efforts to curb epidemics, and will rely on similar strategies to combat obesity. We argue that interventions targeted at youth are relatively easy to justify on economic grounds due to the additional protections that this group requires, but that justification for government interventions aimed at curbing obesity among adults requires additional evidence that private markets are not functioning properly. We then present seven proposed intervention strategies to promote healthy eating, and use an economic framework to discuss the relative merits of the interventions. This evaluation will allow policymakers to make more informed decisions concerning the relative merits of these strategies in combating the obesity epidemic.

This study provides estimates of the economic cost of intimate partner violence perpetrated against women in the US, including expenditures for medical care and mental health services, and lost productivity from injury and premature death. The analysis uses national survey data, including the National Violence Against Women Survey and the Medical Expenditure Panel Survey, to estimate costs for 1995. Intimate partner violence against women cost $5.8 billion dollars (95% confidence interval: $3.9 to $7.7 billion) in 1995, including $320 million ($136 to $503 million) for rapes, $4.2 billion ($2.4 to $6.1 billion) for physical assault, $342 million ($235 to $449 million) for stalking, and $893 million ($840 to $946 million) for murders. Updated to 2003 dollars, costs would total over $8.3 billion. Intimate partner violence is costly in the US. The potential savings from efforts to reduce this violence are substantial. More comprehensive data are needed to refine cost estimates and monitor costs over time.

Direct-current electric fields mediate motility (galvanotaxis) of many cell types. In 3T3 fibroblasts, electric fields increased the proportion, speed and cathodal directionality of motile cells. Analogous to fibroblasts' spontaneous migration, we initially hypothesized that reorientation of microtubule components modulates galvanotaxis. However, cells with intact microtubules did not reorient them in the field and cells without microtubules still migrated, albeit slowly, thus disproving the hypothesis. We next proposed that, in monolayers wounded and placed in an electric field, reorientation of microtubule organizing centers and stable, detyrosinated microtubules towards the wound edge is necessary and/or sufficient for migration. This hypothesis was negated because field exposure mediated migration of unoriented, cathode-facing cells and curtailed migration of oriented, anode-facing cells. This led us to propose that ablating microtubule detyrosination would not affect galvanotaxis. Surprisingly, preventing microtubule detyrosination increased motility speed, suggesting that detyrosination inhibits galvanotaxis. Microtubules might enhance adhesion/de-adhesion remodeling during galvanotaxis; thus, electric fields might more effectively mediate motility of cells poorly or dynamically attached to substrata. Consistent with this hypothesis, incompletely spread cells migrated more rapidly than fully spread cells. Also, overexpression of PAK4, a Cdc42-activated kinase that decreases adhesion, enhanced galvanotaxis speed, whereas its lack decreased speed. Thus, electric fields mediate fibroblast migration via participation of microtubules and adhesive components, but their participation differs from that during spontaneous motility.

Objective: To study how payment for specialty services affects the rates of performance of invasive procedures by physicians in a number of specialties., Study Design: Observational study., Patients and Methods: Administrative data from 1996-1997 and 1997-1998 from 3 large health maintenance organizations (HMOs) in the Midwestern and western United States were used to study variations in procedure rates associated with different methods of paying for cardiology, gastroenterology, ophthalmology, orthopedic, and ear, nose and throat services within each HMO. The age-, sex-, and comorbidity adjusted probabilities of undergoing selected, potentially discretionary procedures, were compared within each plan by payment method., Results: After adjustment, rates under fee-for-service payment tended to be higher than those under capitation or salary payment, whereas there was no clear pattern for salary versus capitation payment. Even within a single specialty in a single plan, however, rates did not always follow the same pattern for different procedures., Conclusions: The payment method for specialty services used by these 3 health plans was variably associated with how likely patients were to undergo a variety of invasive procedures. The effects of contract payment methods for specialty services on health care costs, quality, and outcomes should be further studied, but such studies will challenge the capabilities of health plan data systems.

The liver preferentially secretes alpha-tocopherol into plasma under the control of the hepatic alpha-tocopherol transfer protein (alpha-TTP). alpha-TTP-null mice (Ttpa(-/-) mice) are vitamin E deficient, therefore were used for investigations of in vivo responses to sub-normal tissue alpha-tocopherol concentrations during inflammation. Increased basal oxidative stress in Ttpa(-/-) mice was documented by increased plasma lipid peroxidation, and superoxide production by bone marrow-derived neutrophils stimulated in vitro with phorbol 12-myristate 13-acetate. Lipopolysaccharide (LPS) injected intraperitoneally induced increases in lung and liver HO-1 and iNOS, as well as plasma NO(x) in Ttpa(+/+) mice. LPS induced more modest increases in these markers in Ttpa(-/-) mice, while more marked increases in plasma IL-10 and lung lavage TNF alpha were observed. Taken together, these results demonstrate that alpha-tocopherol is important for proper modulation of inflammatory responses and that sub-optimal alpha-tocopherol concentrations may derange inflammatory-immune responses.

Neural transplantation is an attractive strategy for diseases that result in focal neurodegeneration such as Parkinson's disease, where there is a selective loss of dopaminergic neurons in the substantia nigra of the midbrain. A major drawback to its application, however, is the poor survival of donor dopaminergic neurons. While neurons probably depend on host-derived substances delivered by either diffusion or the establishment of functional vascular connections, the relative importance of each delivery mechanism is not known. We investigated the topography of transplants of embryonic mesencephalic tissue and describe the spatial relationships between transplanted dopaminergic neurons, the host brain, and in-growing blood vessels. Results indicate that transplant vascularization shares features with developmental patterns of brain vascularization. Moreover, the topographical distribution of dopaminergic neurons reflected their proximity to the host brain as well as their distance from vascular elements. Zonal analysis revealed that the majority of dopaminergic neurons were found at or near the host-transplant interface at 1 week after transplantation. Nearest neighbor analysis demonstrated a descending exponential gradient of dopaminergic neurons as a function of their distance from vessels at the same time point. These patterns became more marked with time. Results suggest that rates and patterns of vascularization may be important determinants in the long-term survival of dopaminergic neurons.

Acrolein is a highly reactive unsaturated hazardous air pollutant of human health concern, particularly as a component of cigarette smoke. In this study, the mechanisms of acrolein-induced cytotoxicity in human bronchial epithelial cells (HBE1) and the modulating effects of antioxidants were examined. Our results show that acrolein induces a cell death pathway in human bronchial epithelial cells, which retain key features of apoptosis, as indicated by phosphatidylserine (PS) externalization and DNA fragmentation. Acrolein-induced apoptosis was associated with depletion of cellular GSH and intracellular generation of oxidants. Supplementation of cells with either alpha-tocopherol or ascorbic acid was found to strongly inhibit acrolein-induced apoptosis and to prevent the increase in the generation of intracellular oxidants, although GSH depletion was unaffected. Moreover, recovery of cellular GSH levels after acrolein exposure was enhanced following either alpha-tocopherol or ascorbic acid supplementation. The intracellular generation of oxidants following acrolein exposure seems to be an important event triggering the apoptotic response in this model system.

Cigarette smoking is known to contribute to inflammatory diseases of the respiratory tract by promoting recruitment of inflammatory-immune cells such as neutrophils and perhaps by altering neutrophil functional properties. We investigated whether acrolein, a toxic unsaturated aldehyde found in cigarette smoke, could directly affect neutrophil function. Exposure of freshly isolated human neutrophils to acrolein markedly inhibited spontaneous neutrophil apoptosis as indicated by loss of membrane asymmetry and DNA fragmentation and induced increased neutrophil production of the chemokine interleukin-8 (IL-8). Acrolein (1--50 microM) was found to induce marked activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinases (MAPKs), and inhibition of p38 MAPK activation by SB-203580 prevented acrolein-induced IL-8 release. However, inhibition of either ERK or p38 MAPK did not affect acrolein-dependent inhibition of apoptosis. Acrolein exposure prevented the activation of caspase-3, a crucial step in the execution of neutrophil apoptosis, presumably by direct inhibition of the enzyme. Our results indicate that acrolein may contribute to smoke-induced inflammatory processes in the lung by increasing neutrophil recruitment and reducing neutrophil clearance by apoptosis.

CMS has recently launched a series of initiatives to control Medicare spending on durable medical equipment (DME) and prosthetics, orthotics, and supplies (DMEPOS). An important question is how these initiatives will affect beneficiary satisfaction. Using survey data, we analyze Medicare beneficiary satisfaction with DMEPOS suppliers in two Florida counties. Our results show that beneficiaries are currently highly satisfied with their DMEPOS suppliers. Beneficiary satisfaction is positively related to rapid delivery, training, dependability, and frequency of service. Results of our analysis can be used as baseline estimates in evaluating CMS initiatives to reduce Medicare payments for DMEPOS.

The embryonic vasculature forms by the processes of vasculogenesis and angiogenesis. Angioblasts (endothelial cell precursors) appear to be induced by fibroblast growth factor 2 (FGF-2). The angioblasts contributing to the dorsal aortae arise by an epithelial to mesenchymal transformation of cells originating from the splanchnic mesoderm. QH-l and vascular endothelial growth factor receptor 2 (VEGFR-2) both appear to label these cells as they adopt a mesenchymal morphology. Since VEGFR-2 is the earliest known VEGF receptor this suggests that VEGF is not involved in angioblast induction. VEGF does appear to be critical, however, for growth and morphogenesis of angioblasts into the initial vascular pattern. Controlled delivery of FGF-2 from beads and aggregates of cells transfected with quail VEGF have been used in our laboratory to study the role of these growth factors in angioblast induction and migration. We have induced cells from the epithelial quail somite to differentiate into angioblasts with FGF-2 both in the embryo and in culture. This is a useful model system to study the origins of endothelial cells that are normally more diffusely induced during gastrulation by an obscure process probably involving signals from the embryonic endoderm. The origins of arterial versus venous endothelial cells is also poorly understood but recent findings on the distribution of ephrins and Eph receptors suggest that molecular differences exist prior to the onset of circulation. Finally, studies on the role of growth factors in such diverse phenomena as stem cell biology, angiogenesis, and molecular medicine in addition to vascular development suggest multiple roles for FGF-2 and VEGF in vascular development., (Copyright 2001 Wiley-Liss, Inc.)

An increased risk for a second malignancy has been reported in patients with mycosis fungoides. We describe two subjects with mycosis fungoides who developed small malignant melanoma after topical application of nitrogen mustard.

Surgical therapy remains the only curative treatment of localized non-small cell lung carcinoma (NSCLC). Yet, the results of surgical therapy leave much to be desired. Recently, neoadjuvant chemotherapy for Stage III NSCLC had become an accepted therapeutic modality. Accordingly, a question is raised regarding the feasibility of neoadjuvant chemotherapy in resectable NSCLC (Stage I and II). In this paper we report three patients, in chronological order, with localized NSCLC who were treated with neoadjuvant chemotherapy. Neoadjuvant chemotherapy was given to the first case with poor pulmonary functions. Decrease in size of the tumor made it possible for him to undergo a more conservative lung resection. In the second case, chemotherapy was given with a presumptive diagnosis of metastatic lung lesion. A good response was noted and, histologically, it was a primary lung cancer. In the third case, chemotherapy was given to a patient with obviously resectable lung carcinoma, and an excellent response was observed. According to the results, neoadjuvant chemotherapy for resectable NSCLC may be feasible and beneficial.

In order to establish a possible relationship between keratosis lichenoides chronica (KLC) and lichen planus (LP), we performed a comparative study which included routine histologic examination, electron microscopy, and direct immunohistochemical studies from one case of KLC and several patients with LP. Our findings demonstrate that KLC and LP share many similarities; their differences are mostly quantitative. In KLC, the findings are more prominent; we therefore conclude that KLC is at one end of the spectrum of LP.

Belgrade rats inherit microcytic, hypochromic anemia as an autosomal recessive trait (gene symbol b). Erythrocytes and tissue are iron deficient in the face of elevated TIBC (total iron binding capacity) and percent iron saturation; iron injections increased the number of erythrocytes but their appearance remained abnormal. We have investigated iron supplements to improve husbandry of b/b rats and to learn more about the underlying defect and its tissue distribution. Weekly i.m. (intramuscular) injections of iron-dextran (Imferon at 30 mg kg-1) improved the anemia but did not alter the red cell morphology. Certain diets also improved the health of b/b rats when compared to standard rat chows by the criteria of weight, survival to adulthood, hematology and reproduction. The critical nutritional factor turned out to be iron bioavailability, with ferrous iron added to the diet improving the health of Belgrade rats without affecting the underlying erythroid defect. Tissue iron measurements after dietary or parenteral supplementation confirmed the iron deficient status of untreated b/b rats and established that dietary ferrous iron partially relieved this deficiency, with injections leading to greater amounts of tissue iron. Serum iron and TIBC were also found to be elevated in untreated b/b rats, with dietary supplementation decreasing but not eliminating the elevation in TIBC. These studies indicate that iron supplements can improve the health of b/b rats without altering the underlying defect and also suggest that the mutation could alter iron uptake in the GI (gastrointestinal) tract.

Esophageal involvement in pemphigus vulgaris is rare, found more in women than in men, and can be the only manifestation of pemphigus. Esophageal involvement had been reported only among patients with pemphigus vulgaris and not in patients with other forms of pemphigus. We describe a case of pemphigus vulgaris in which the esophagus was severely involved with only few oral lesions and no involvement of the skin or oropharynx.

A patient with both vitiligo and morphea is described. These skin diseases rarely appear concurrently in the same patient, despite the fact that both are thought to an autoimmune etiology. Similar cases that have been reported in the literature are reviewed and discussed.

A classical case of Werner's syndrome is described. In addition to the numerous skin changes that are typically associated with Werner's syndrome, our patients also displayed diffuse lentiginosis, and several of the clinical features of leopard syndrome. Histopathological and ultrastructural findings from a hyperpigmented macule displayed the typical features of a simple lentigo. A striking feature was the presence of melanosomes in Langerhans cells as has been reported in the leopard syndrome. A possible generalized mesodermal defect has been suggested in Werner's syndrome, while the basic defect in the leopard syndrome is thought to be of neuroectodermal origin with pleiotropic changes in the organs derived from the mesoderm. Our patient, with incomplete leopard syndrome and typical Werner's syndrome, may be an example of an association of genetic defects affecting both tissues of neuroectodermal and mesodermal origin.

Background: Celery is known to contain psoralens, a group of substances that cause a toxic dermal reaction on exposure to ultraviolet A rays (UVA). An outbreak of phytophotodermatitis amongst 11 workers in a celery harvest in southern Israel is reported., Methods: Analysis of the trigger factors was carried out. The patients were questioned regarding their working conditions. Samples of the celery that the workers had been harvesting were analyzed for levels of total psoralens by means of high performance liquid chromatography (HPLC). Levels of UVA were measured., Results: It was found that the celery harvested in the south of the country contained 84 micrograms/g fresh weight (f.wt.) total psoralens as compared to 35 micrograms/g f.wt. in celery harvested in the north of the country at the same time. The following year the celery harvested in the south contained only 26 micrograms/g f.wt. total psoralens. Other risk factors noted were that the subjects had fair skin, wore no protective clothing, and worked with moist hands. In addition, the days were clear and sunny thus ensuring maximal UV radiation for that time of the year., Conclusions: Multiple factors contributed to the outbreak of phytophotodermatitis. A late harvest in the south of the country is incriminated as the cause of the unusually high levels of psoralens in the celery of that year.

Cutaneous leishmaniasis is now seen in non-endemic areas, especially in travellers to and troops serving in the Middle East. It was a common problem among American troops returning from the Gulf war. This article presents the clinical manifestations, the laboratory findings and the treatment options for this disease.

Hypomelanosis of Ito is an uncommon syndrome where bizarre, systematized hypopigmentation is often associated with neurological and other non-cutaneous abnormalities. We report two cases, one which was associated with laryngomalacia and sudden death (in which the parents were consanguineous), and one which was associated with episodes of loss of consciousness.

Stable nitroxide radicals have been previously shown to function as superoxide dismutase (SOD)2 mimics and to protect mammalian cells against superoxide and hydrogen peroxide-mediated oxidative stress. These unique characteristics suggested that nitroxides, such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), might protect mammalian cells against ionizing radiation. Treating Chinese hamster cells under aerobic conditions with 5, 10, 50, and 100 mM Tempol 10 min prior to X-rays resulted in radiation protection factors of 1.25, 1.30, 2.1, and 2.5, respectively. However, the reduced form of Tempol afforded no protection. Tempol treatment under hypoxic conditions did not provide radioprotection. Aerobic X-ray protection by Tempol could not be attributed to the induction of intracellular hypoxia, increase in intracellular glutathione, or induction of intracellular SOD mRNA. Tempol thus represents a new class of non-thiol-containing radiation protectors, which may be useful in elucidating the mechanism(s) of radiation-induced cellular damage and may have broad applications in protecting against oxidative stress.