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Background: A recent trial showed that postmenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor-2 (HER2)-negative, lymph node-positive (1-3 nodes) breast cancer with a 21-gene recurrence score of ≤ 25 could safely omit chemotherapy. However, there are limited data on population-level long-term outcomes associated with omitting chemotherapy among diverse women seen in real-world practice., Methods: We adapted an established, validated simulation model to generate the joint distributions of population-level characteristics of women diagnosed with early-stage breast cancer in the U.S. Input parameters were derived from cancer registry, meta-analyses, and clinical trial data. The effects of omitting chemotherapy on 10-year distant recurrence-free survival, life-years, and quality adjusted life-years (QALYs) were modeled for premenopausal and postmenopausal women. QALYs were discounted at 3%. Results were evaluated for subgroups stratified by race and ethnicity. Sensitivity analyses included testing results across a range of inputs. The model was validated using the published RxPONDER trial data., Results: In premenopausal women, the 10-year distant recurrence-free survival rates were 85.3% with chemo-endocrine and 80.1% with endocrine therapy. The estimated life-years and QALYs gained with chemotherapy in premenopausal women were 2.1 and 0.6, respectively. There was no chemotherapy benefit in postmenopausal women. There was no variation in the absolute benefit of chemotherapy across racial or ethnic subgroups. However, there were differences in distant recurrence-free survival rates, life-years, and QALYs across groups. Sensitivity analysis showed similar results. The model closely replicated the RxPONDER trial., Conclusions: Modeled population-level outcomes show a small chemotherapy benefit in premenopausal women, but no benefit among postmenopausal women. Simulation modeling provides a useful tool to extend trial data and evaluate population-level outcomes., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Immune-related endocrinopathies are common after immune checkpoint inhibitor (ICI) therapy, among which destructive thyroiditis is the most prevalent. Improved survival outcomes have been associated with immune-related adverse events. We aimed to compare the clinical course and biochemical parameters of two subtypes of ICI-related destructive thyroiditis: a transient thyrotoxicosis that reverts to either euthyroidism (TT; transient thyroiditis) versus progression to permanent hypothyroidism (PH), and to identify prognostic markers in cancer patients receiving ICI therapy who developed DT., Methods: This retrospective observational study included 124 patients who developed a transient thyrotoxicosis due to a destructive thyroiditis after ICI therapy from January 1, 2016 to April 30, 2021 at the Montefiore Medical Center. Patients were categorized as either TT or PH based on spontaneous renormalization of the TSH or the permanent need for thyroid hormone replacement, respectively. Thyroid hormone and antibody levels, serum inflammatory markers, eosinophils, and metabolic uptake of the thyroid on PET imaging, each corresponding closest to a suppressed TSH, were characterized. Survival from TT and PH were also analyzed., Results: Of the 124 patients, 53 developed PH and 71 developed TT. The PH group developed thyrotoxicosis at a median of 42 days from the first ICI dose while the TT group took significantly longer at 56 days. Thyroidal PET uptake was increased in 18.9% of the PH group versus 6.0% of the TT group (P=0.04). Three different survival models consistently demonstrated a trend towards increased survival in the PH group, compared to the TT group., Conclusion: Our results suggest that PH developing after ICI-induced destructive thyroiditis may be associated with a more robust inflammatory and antitumor response to ICI therapy. The results suggests that PH may be a potential clinical predictor of improved survival., Competing Interests: YT declares that he was previously 1/2015 - 6/2017 the principal investigator on a basic research project jointly funded by the Juvenile Diabetes Research Foundation and Pfizer. The current manuscript is not related to that research project. YT has a patent and patent applications that are not related to the content of this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Manavalan, Stefan-Lifshitz, Schechter, Maity and Tomer.)

Objective: Diabetes and the outpatient diabetes treatment regimen have been identified as risk factors for poor outcomes in patients with sepsis. However, little is known about the effect of tight inpatient glycemic control in the setting of coronavirus disease 2019 (COVID-19). Therefore, we examined the effect of hyperglycemia in patients with diabetes hospitalized because of COVID-19., Research Design and Methods: We analyzed data from 1,938 COVID-19 patients with diabetes hospitalized for COVID-19 from March to May 2020 at a large academic medical center in New York City. Patients were divided into two groups based on their inpatient glycemic values, and a Cox proportional hazards regression model was used to assess the independent association of inpatient glucose levels with mortality (primary outcome) and the risk of requiring mechanical ventilation (MV) (secondary outcome)., Results: In our analysis, 32% of the patients were normoglycemic and 68% hyperglycemic. Moreover, 31% of the study subjects died during hospitalization, and 14% required MV, with inpatient hyperglycemia being significantly associated with both mortality and the requirement for MV. Additionally, in the Cox regression analysis, after adjustment for potential confounders, including age, sex, race, BMI, HbA1c, comorbidities, inflammatory markers, and corticosteroid therapy, patients with uncontrolled hyperglycemia had a higher risk of dying (hazard ratio [HR] 1.54, 95% CI 1.00-2.36, P = 0.049) and of requiring MV (HR 4.41, 95% CI 1.52-2.81, P = 0.006) than those with normoglycemia., Conclusions: A tight control of inpatient hyperglycemia may be an effective method for improving outcomes in patients with diabetes hospitalized for COVID-19., (© 2022 by the American Diabetes Association.)

Background: Extending endocrine therapy from 5 to 10 years is recommended for women with invasive estrogen receptor (ER)-positive breast cancers. We evaluated the benefits and harms of the five additional years of therapy., Methods: An established Cancer Intervention and Surveillance Network (CISNET) model used a lifetime horizon with national and clinical trial data on treatment efficacy and adverse events and other-cause mortality among multiple birth cohorts of U.S. women ages 25-79 newly diagnosed with ER+, non-metastatic breast cancer. We assumed 100% use of therapy. Outcomes included life years (LYs), quality-adjusted life years (QALYs), and breast cancer mortality. Results were discounted at 3%. Sensitivity analyses tested a 15-year time horizon and alternative assumptions., Results: Extending tamoxifen therapy duration among women ages 25-49 reduced the lifetime probability of breast cancer death from 11.9% to 9.3% (absolute difference 2.6%). This translates to a gain of 0.77 LYs (281 days)/woman (undiscounted). Adverse events reduce this gain to 0.44 QALYs and after discounting, gains are 0.20 QALYs (73 days)/woman. Extended aromatase inhibitor therapy in women 50-79 had small absolute benefits and gains were offset by adverse events (loss of 0.06 discounted QALYs). There were greater gains with extended endocrine therapy for women with node-positive versus negative cancers, but only women ages 25-49 and 50-59 had a net QALY gain. All gains were reduced with less than 100% treatment completion., Conclusion: The extension of endocrine therapy from 5 to 10 years modestly improved lifetime breast cancer outcomes, but in some women, treatment-related adverse events may outweigh benefits., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To examine whether HbA 1c , outpatient diabetes treatment regimen, demographics, and clinical characteristics are associated with mortality in hospitalized patients with diabetes and coronavirus disease 2019 (COVID-19)., Research Design and Methods: This was a retrospective cohort analysis of patients with diabetes hospitalized with confirmed COVID-19 infection from 11 March to 7 May 2020 at a large academic medical center in New York City. Multivariate modeling was used to assess the independent association of HbA 1c levels and outpatient diabetes treatment regimen with mortality, in addition to independent effects of demographic and clinical characteristics., Results: We included 1,126 hospitalized patients with diabetes and COVID-19 for analysis, among whom mean age was 68 years, 50% were male, 75% were Black, mean BMI was 30 kg/m 2 , 98% had type 2 diabetes, mean HbA 1c was 7.5%, and 33.1% died. HbA 1c levels were not associated with mortality in unadjusted or adjusted analyses, but an outpatient regimen with any insulin treatment was strongly predictive. Additionally, age, sex, and BMI interacted such that in all age categories, mortality was higher with increasing BMI in males compared with females., Conclusions: In this large U.S. cohort of hospitalized patients with diabetes and COVID-19, insulin treatment, as a possible proxy for diabetes duration, and obesity rather than long-term glycemic control were predictive of mortality. Further investigation of underlying mechanisms of mortality and inpatient glycemic control is needed., (© 2020 by the American Diabetes Association.)

Objectives: The objective was to assess the efficacy of patient-controlled analgesia (PCA) in the emergency department (ED) and to compare two PCA dosing regimens., Methods: A randomized controlled trial with three treatment arms was performed in an urban ED. A convenience sample of ED patients ages 18 to 65 years with abdominal pain of 7 days or less duration requiring intravenous (IV) opioid analgesia was enrolled between April 2009 and June 2010. All patients received an initial dose of 0.1 mg/kg IV morphine followed by physician-managed analgesia as needed. Patients in the PCA arms also received IV morphine with on-demand doses of 1 or 1.5 mg, with a 6-minute lockout between doses. Pain intensity was rated by patients on an 11-point numeric rating scale (NRS). Satisfaction with pain treatment, desire for the same treatment in the future, and need for additional analgesia were assessed at study end. Adverse events (O(2) sat < 92%, respiratory rate [RR] < 10/min, systolic blood pressure [sBP] < 90 mm Hg, and naloxone use) were counted. One-way analysis of variance was used to test the difference among groups in short-term pain relief, as assessed by mean change in NRS pain intensity from baseline to 30 minutes and pain over the entire 2-hour study period measured by area under the curve (AUC) of NRS pain ratings. A post hoc hierarchical linear model was used to test the observed difference in NRS between the groups between 30 and 120 minutes., Results: A total of 211 patients were enrolled. A sharp, nearly identical decline in mean NRS scores occurred from baseline to 30 minutes in the three groups (p = 0.82). Between 30 and 120 minutes, there was little further decline in the non-PCA NRS scores, while both PCA groups continued to decline (p = 0.004). The net treatment effect over the entire 2 hours was smallest in the non-PCA group and largest in the group receiving 1.5 mg of morphine (p = 0.06). The mean decline in pain from baseline to 120 minutes postbaseline in both PCA groups was 1.4 NRS units (95% confidence interval [CI] = 0.3 to 2.4) greater than the decline in patients treated without PCA. More patients in the PCA arms reported satisfaction, wanting the same pain management in the future, and not wanting further analgesics at 120 minutes than patients who did not receive PCA. There were no clinically or statistically significant differences in any outcomes between the two PCA groups. One PCA patient had a transient oxygen saturation of 88% after the initial bolus only, and one non-PCA patient had a brief drop in sBP to 87 mm Hg., Conclusions: This study provides support for efficacy of PCA when applied to the ED setting. Future studies designed to assess implementation of this modality in the context of conditions of actual ED staffing and competing patient demands are warranted., (© 2012 by the Society for Academic Emergency Medicine.)

Deep inspirations modulate airway caliber and airway closure and their effects are impaired in asthma. The association between asthma and obesity raises the question whether the deep inspiration (DI) effect is also impaired in the latter condition. We assessed the DI effects in obese and nonobese nonasthmatics. Thirty-six subjects (17 obese, 19 nonobese) underwent routine methacholine (Mch) challenge and 30 of them also had a modified bronchoprovocation in the absence of DIs. Lung function was monitored with spirometry and forced oscillation (FO) [resistance (R) at 5 Hz (R5), at 20 Hz (R20), R5-R20 and the integrated area of low-frequency reactance (AX)]. The response to Mch, assessed with area under the dose-response curves (AUC), was consistently greater in the routine challenge in the obese (mean ± SE, obese vs. nonobese AUC: R5: 15.7 ± 2.3 vs. 2.4 ± 2.0, P < 0.0005; R20: 5.6 ± 1.4 vs. 1.4 ± 1.2, P = 0.027; R5-R20: 10.2 ± 1.6 vs. 0.9 ± 0.1.4, P < 0.0005; AX: 115.6 ± 22.0 vs. 1.5 ± 18.9, P < 0.0005), but differences between groups in the modified challenge were smaller, indicating reduced DI effects in obesity. Given that DI has bronchodilatory and bronchoprotective effects, we further assessed these components separately. In the obese subjects, DI prior to Mch enhanced Mch-induced bronchoconstriction, but DI after Mch resulted in bronchodilation that was of similar magnitude as in the nonobese. We conclude that obesity is characterized by increased Mch responsiveness, predominantly of the small airways, due to a DI effect that renders the airways more sensitive to the stimulus.

Social Security is the most important and effective income support program ever introduced in the United States, alleviating the burden of poverty for millions of elderly Americans. We explored the possible role of Social Security in reducing mortality among the elderly. In support of this hypothesis, we found that declines in mortality among the elderly exceeded those among younger age groups following the initial implementation of Social Security in 1940, and also in the periods following marked improvements in Social Security benefits via legislation and indexing of benefits that occurred between the mid-1960s and the early 1970s. A better understanding of the link between Social Security and health status among the elderly would add a significant and missing dimension to the public discourse over the future of Social Security, and the potential role of income support programs in reducing health-related socioeconomic disparities and improving population health.

Racial and ethnic disparities in obesity persist despite a narrowing in obesity risk associated with socioeconomic status. The household environment has been shown to be important in understanding obesity-promoting behaviors in diverse populations. Our current study was designed to examine the relationship between household density and obesity in young Black and White adults aged 18-30 years from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. All sociodemographic and leisure-time physical activity (LTPA) information for this study was collected by questionnaire between 1990-1991. Height was collected using a mounted centimeter ruler. Weight was measured on a balance beam scale. Obesity was defined as a body mass index > or = 30 kg/m2. Household density (HD) was defined as the ratio of people to bedrooms in the home. High HD was defined as a ratio > 1. Bivariate analysis showed that more women tend to live in high density households compared to men (45.4% vs 38.9%; P < .01) and more Blacks tend to live in high density households compared to Whites (53.7% vs 31.8%). Leisure-time physical activity index was lower in Blacks than in Whites (2.5% vs 2.6%; P < .01). Blacks had a higher prevalence of obesity than Whites (27.1% vs 11.8%; P < .01). Logistic regression analysis showed that Black women within high HD were at highest risk for obesity compared to White women living within low HD (OR = 4.88%; 95% CI: 3.56-6.67). HD may provide an important context in understanding racial disparities in obesity-promoting behaviors.

Objective: To compare the effects of a 1-year intervention with a low-carbohydrate and a low-fat diet on weight loss and glycemic control in patients with type 2 diabetes., Research Design and Methods: This study is a randomized clinical trial of 105 overweight adults with type 2 diabetes. Primary outcomes were weight and A1C. Secondary outcomes included blood pressure and lipids. Outcome measures were obtained at 3, 6, and 12 months., Results: The greatest reduction in weight and A1C occurred within the first 3 months. Weight loss occurred faster in the low-carbohydrate group than in the low-fat group (P = 0.005), but at 1 year a similar 3.4% weight reduction was seen in both dietary groups. There was no significant change in A1C in either group at 1 year. There was no change in blood pressure, but a greater increase in HDL was observed in the low-carbohydrate group (P = 0.002)., Conclusions: Among patients with type 2 diabetes, after 1 year a low-carbohydrate diet had effects on weight and A1C similar to those seen with a low-fat diet. There was no significant effect on blood pressure, but the low-carbohydrate diet produced a greater increase in HDL cholesterol.

The principal objective of our research is to examine whether the earned income tax credit (EITC), a broad-based income support program that has been shown to increase employment and income among poor working families, also improves their health and access to care. A finding that the EITC has a positive impact on the health of the American public may help guide deliberations about its future at the federal, state, and local levels. The authors contend that a better understanding of the relationship between major socioeconomic policies such as the EITC and the public's health will inform the fields of health and social policy in the pursuit of improving population health.

Background: Breast cancer surgery is associated with side effects, including postsurgical pain, nausea, and fatigue. We carried out a randomized clinical trial to test the hypotheses that a brief presurgery hypnosis intervention would decrease intraoperative anesthesia and analgesic use and side effects associated with breast cancer surgery and that it would be cost effective., Methods: We randomly assigned 200 patients who were scheduled to undergo excisional breast biopsy or lumpectomy (mean age 48.5 years) to a 15-minute presurgery hypnosis session conducted by a psychologist or nondirective empathic listening (attention control). Patients were not blinded to group assignment. Intraoperative anesthesia use (i.e., of the analgesics lidocaine and fentanyl and the sedatives propofol and midazolam) was assessed. Patient-reported pain and other side effects as measured on a visual analog scale (0-100) were assessed at discharge, as was use of analgesics in the recovery room. Institutional costs and time in the operating room were assessed via chart review., Results: Patients in the hypnosis group required less propofol (means = 64.01 versus 96.64 microg; difference = 32.63; 95% confidence interval [CI] = 3.95 to 61.30) and lidocaine (means = 24.23 versus 31.09 mL; difference = 6.86; 95% CI = 3.05 to 10.68) than patients in the control group. Patients in the hypnosis group also reported less pain intensity (means = 22.43 versus 47.83; difference = 25.40; 95% CI = 17.56 to 33.25), pain unpleasantness (means = 21.19 versus 39.05; difference = 17.86; 95% CI = 9.92 to 25.80), nausea (means = 6.57 versus 25.49; difference = 18.92; 95% CI = 12.98 to 24.87), fatigue (means = 29.47 versus 54.20; difference = 24.73; 95% CI = 16.64 to 32.83), discomfort (means = 23.01 versus 43.20; difference = 20.19; 95% CI = 12.36 to 28.02), and emotional upset (means = 8.67 versus 33.46; difference = 24.79; 95% CI = 18.56 to 31.03). No statistically significant differences were seen in the use of fentanyl, midazolam, or recovery room analgesics. Institutional costs for surgical breast cancer procedures were $8561 per patient at Mount Sinai School of Medicine. Patients in the hypnosis group cost the institution $772.71 less per patient than those in the control group (95% CI = 75.10 to 1469.89), mainly due to reduced surgical time., Conclusions: Hypnosis was superior to attention control regarding propofol and lidocaine use; pain, nausea, fatigue, discomfort, and emotional upset at discharge; and institutional cost. Overall, the present data support the use of hypnosis with breast cancer surgery patients.

Chronic diseases of environmental origin are a significant and increasing public health problem among the children of New York State, yet few resources exist to address this growing burden. To assess New York State pediatricians self-perceived competency in dealing with common environmental exposures and diseases of environmental origin in children, we assessed their attitudes and beliefs about the role of the environment in children's health. A four-page survey was sent to 1,500 randomly selected members of the New York State American Academy of Pediatrics in February 2004. We obtained a 20.3% response rate after one follow-up mailing; respondents and nonrespondents did not differ in years of licensure or county of residence. Respondents agreed that the role of environment in children's health is significant (mean 4.44 +/- 0.72 on 1-5 Likert scale). They voiced high self-efficacy in dealing with lead exposure (mean 4.16-4.24 +/- 0.90-1.05), but their confidence in their skills for addressing pesticides, mercury and mold was much lower (means 2.51-3.21 +/- 0.90-1.23; p < 0.001). About 93.8% would send patients to a clinic "where pediatricians could refer patients for clinical evaluation and treatment of their environmental health concerns." These findings indicate that New York pediatricians agree that children are suffering preventable illnesses of environmental origin but feel ill-equipped to educate families about common exposures. Significant demand exists for specialized centers of excellence that can evaluate environmental health concerns, and for educational opportunities.

Unlabelled: The purpose of the present study was to prospectively investigate the extent to which emergency providers base their decisions about pain management of suspected long-bone fracture on patient's self-reported pain intensity. Of 100 long-bone fracture patients presenting to 2 inner-city emergency departments, 69% received opioids as compared to 30% of 110 patients without long-bone fracture (RR = 2.3; 95% CI 1.6 to 3.1). After stratification by pain ratings on a validated self-reported numerical rating scale, fracture patients remained twice as likely to receive opioids as those without fracture (RR = 2.0; 95% CI 1.5 to 2.7). Similarly, multivariate adjustment for self-reported pain intensity had little effect on the observed association (RR = 2.1; 95% CI 1.6 to 2.8). We conclude that emergency providers do not primarily base their decisions about pain management of suspected long-bone fractures on patient self-reporting of pain intensity., Perspective: This article addresses the question of the role of self-reported pain intensity rating on the treatment of suspected fractures. The findings indicate that self-reported pain is not used as the most important measure of pain as recommended by expert panels. We speculate this may contribute to oligoanalgesia in the Emergency Department.

Unlabelled: There is some evidence from in vitro, animal, and postoperative clinical studies that low doses of opioid antagonists combined with morphine increase analgesia. The theoretical model of this effect posits that ultra-low doses of opioid antagonists selectively antagonize excitatory, but not inhibitory, opioid receptor-mediated signaling. To determine whether this effect occurs in emergency department patients presenting with severe acute pain, we conducted a randomized, double-blind placebo-controlled trial to assess the relative analgesic effect of morphine administered with 3 different doses of naloxone versus morphine alone. Patients received 0.1 mg/kg morphine intravenously (IV) over 2 min plus one of 3 different doses of naloxone (0.1 ng/kg, 0.01 ng/kg, or 0.001 ng/kg) or normal saline. A 0 to 10 numerical rating scale (NRS) was used to measure pain intensity at baseline and every 30 min up to 4 hours. One hundred fifty-six patients with a median NRS of 10 (IQR: 8-10) were studied. There were no clinically or statistically significant differences in the mean pain intensity of patients in the 4 treatment groups over the 4-hour study period, nor were there differences in the administration of additional analgesics or incidence of side effects., Perspective: Ultra-low doses of naloxone in the 0.001 ng/kg to 0.1 ng/kg range do not enhance the analgesia provided by morphine alone among emergency department patients with acute, severe pain. This suggests that naloxone in these doses is not an effective adjunct to morphine for control of acute pain.

Clinical trials in peripheral arterial disease (PAD) require an accurate definition of the disease for inclusion; they typically use treadmill testing, questionnaires and hemodynamic measures as primary and secondary endpoints. Trials of new pharmacologic therapies for PAD often employ multiple clinical sites with presumed expertise in the diagnosis and management of PAD as well as in clinical trials. However, considerable variability has been observed in the assessment of endpoints used in PAD trials, as well as a marked placebo response with treadmill testing. This variability and placebo response impact adversely on overall trial integrity, necessitate an inflated sample size, and may contribute to the large number of recently negative claudication trials. We hypothesized that site monitoring visits for evaluating testing methods would identify and characterize several critical issues that would contribute to poor testing quality. One hundred sites participating in three claudication trials for which peak walking time on the treadmill was the primary endpoint, and 16 sites participating in a critical leg ischemia study for which transcutaneous oxygen tension (TcPO2) was the primary endpoint were evaluated. Each site was visited one or more times by a clinical monitor trained in conducting a 'site endpoint evaluation visit' focusing on equipment, physical set-up of the room in which testing was to be conducted, and the site staff's ability to conduct each of the specific measurements. Full reports were generated that covered a number of technical issues for each measurement and data were extracted from these reports to summarize the testing problems encountered at each site. Problems with treadmill testing were common. For example, 92% of sites had problems with their treadmill equipment, 58% did not perform proper treadmill familiarization, 24% did not start the treadmill test appropriately, 24% did not conduct the test properly, and 15% did not properly conclude the test to determine the peak walking time of the participant. Similar problems were encountered with the ankle-brachial index test, the administration of questionnaires and measurement of the TcPO2. Major deficiencies were identified at the majority of sites in the assessment of primary and secondary endpoints in PAD trials. These errors and improper testing provide a potential explanation for the wide variability and placebo responses observed in claudication and critical leg ischemia trials. Site interventions need to address these deficiencies in measurement to improve the quality of PAD trials.

Methyl mercury is a developmental neurotoxicant. Exposure results principally from consumption by pregnant women of seafood contaminated by mercury from anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S. Environmental Protection Agency (EPA) made steady progress in reducing mercury emissions from anthropogenic sources, especially from power plants, which account for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to slow this progress, citing high costs of pollution abatement. To put into perspective the costs of controlling emissions from American power plants, we have estimated the economic costs of methyl mercury toxicity attributable to mercury from these plants. We used an environmentally attributable fraction model and limited our analysis to the neurodevelopmental impacts--specifically loss of intelligence. Using national blood mercury prevalence data from the Centers for Disease Control and Prevention, we found that between 316,588 and 637,233 children each year have cord blood mercury levels > 5.8 microg/L, a level associated with loss of IQ. The resulting loss of intelligence causes diminished economic productivity that persists over the entire lifetime of these children. This lost productivity is the major cost of methyl mercury toxicity, and it amounts to $8.7 billion annually (range, $2.2-43.8 billion; all costs are in 2000 US$). Of this total, $1.3 billion (range, $0.1-6.5 billion) each year is attributable to mercury emissions from American power plants. This significant toll threatens the economic health and security of the United States and should be considered in the debate on mercury pollution controls.

A series of studies have demonstrated that people who live in regions where there are disparities in income have poorer average health status than people who live in more economically homogeneous regions. To test whether such disparities might explain health variations within urban areas, we examined the possible association between income inequality and infant mortality for zip code regions within New York City using data from the 1990 census and the New York City Department of Health. Both infant mortality and income inequality (percentage of income received by the poorest 50% of households) varied widely across these regions (range in infant mortality: 0.6-29.6/1,000 live births; range in income inequality: 12.7-27.3). An increase of one standard deviation in income inequality was associated with an increase of 0.80 deaths/1,000 live births (P <.001), controlling for other socioeconomic factors. This finding has important implications for public health practice and social epidemiological research in large urban areas, which face significant disparities both in health and in social and economic conditions.

HFE is a nonclassical class I molecule that associates with beta 2-microglobulin (beta 2m) and with the transferrin receptor. HFE accumulates in transferrin-containing endosomes, and its overexpression in human cell lines correlates with decreased transferrin receptor (TFR)-mediated iron uptake and decreased intracellular iron pools. A mutation that interferes with proper folding and assembly of HFE complexes results in a severe iron-overload disease hereditary hemochromatosis. We previously suggested that viruses could also interfere with iron metabolism through the production of proteins that inactivate HFE, similarly to classical class I proteins. In particular, we demonstrated in a transient expression system that human cytomegalovirus (HCMV) US2 targeted HFE for proteasomal degradation. Here we demonstrate that the stable expression of HCMV US2 in HEK 293 cells constitutively expressing HFE leads to loss of HFE expression both intracellularly and on the cell surface, and the significant reduction of classical class I expression. Both HFE and classical class I molecules are targeted to degradation via a similar pathway. This HCMV US2-mediated degradation of HFE leads to increased intracellular iron pools as indicated by reduced synthesis of TfR and increased ferritin synthesis. Whether this interference with regulation of iron metabolism potentiates viral replication and/or promotes damage of HCMV-infected tissues remains to be determined. Nevertheless, the deleterious effect of US2 on the expression of HFE and classical class I major histo-compatibility complexes (MHC) provides HCMV with an efficient tool for altering cellular metabolic functions, as well as supporting the escape of virus-infected cells from cytotoxic T lymphocyte (CTL)-mediated immune responses.

Objective: MRI is being used to characterize the composition of atherosclerotic plaques. However, the resolution achievable using surface radiofrequency coils is limited by the signal to noise ratio. We studied the utility of a new intravascular (IV) MRI probe for high-resolution in vivo imaging of atherosclerotic lesions., Methods and Results: Balloon-injured Watanabe heritable hyperlipidemic rabbits served as the experimental model of atherosclerosis. The newly developed IV MRI probe is 1.3 mm in diameter and can be positioned over a guidewire. MRI was performed with both an external phased-array coil and the IV MR coil. MR observations were correlated with histopathology. After MRI, the animals were killed and analysis of agreement between MR and histopathology was performed. The IV MR coil allows aortic images to be obtained with 156x156 micro m(2) in-plane resolution versus 352x352 micro m(2) when used with the external phased-array coil. No significant motion artifacts were noted, despite the continuation of arterial blood flow during image acquisition around the IV probe. The different components of the atherosclerotic lesions (lipid core and fibrous cap) were easily identified. There was an excellent agreement between MRI with the IV coil and histopathology by simple linear regression for both the mean wall thickness (r=0.88, slope 0.82, P<0.0001) and vessel wall area (r=0.86, slope 1.08, P<0.0001)., Conclusions: The new nonobstructive design for this intravascular coil provides great promise for additional work in high-resolution MRI characterization of atherosclerotic plaques in vivo. The ability to position the probe with a guidewire allows its placement under fluoroscopic or MRI guidance, whereas its size is compatible with human coronary arteries.

HFE is a nonclassical class I major histocompatibility complex (MHC) molecule that is mutated in the autosomal recessive iron overload disease hereditary hemochromatosis. There is evidence linking HFE with reduced iron uptake by the transferrin receptor (TfR). Using a panel of HFE and TfR monoclonal antibodies to examine human HFE (hHFE)-expressing cell lines, we demonstrate the expression of stable and fully glycosylated TfR-free and TfR-associated hHFE/beta2m complexes. We show that both the stability and assembly of hHFE complexes can be modified by the human cytomegalovirus (HCMV) viral protein US2, known to interfere with the expression of classical class I MHC molecules. HCMV US2, but not US11, targets HFE molecules for degradation by the proteasome. Whether this interference with the regulation of iron metabolism by a viral protein is a means of potentiating viral replication remains to be determined. The reduced expression of classical class I MHC and HFE complexes provides the virus with an efficient tool for altering cellular metabolism and escaping certain immune responses.

Objective: Our goals were to assess adherence to the National Cancer Institute clinical practice guideline for the management of atypical squamous cells of uncertain significance (ASCUS) Papanicolaou (Pap) test results in a community at high risk of cervical cancer. We also hoped to identify predictors of adherence to the guideline., Study Design: We used an historical cohort and collected data by chart abstraction., Population: Our study included women receiving care in 7 urban community health centers who had an initial ASCUS or atypical Pap test result in 1996. We excluded women with a history of cervical dysplasia or human immunodeficiency virus infection, yielding a final sample of 387 women., Outcomes: measured The outcome measured was the level of adherence to the guideline, defined as falling within 1 of 3 mutually exclusive categories (complete, moderate, or low)., Results: Care providers recommended colposcopy after an initial atypical Pap test result in 12% of cases and repeat cytology in 67%. Failure to document a plan for management was found in 19% of cases. Complete adherence was achieved for 27% of subjects, moderate adherence for 28%, and low adherence for 45%. The factors associated with complete versus moderate or low adherence included site of care, description of the abnormality (ASCUS vs atypia), availability of on-site colposcopy, and discussing the plan at a visit., Conclusions: Adherence with the National Cancer Institute clinical practice guideline in this setting was disappointing and varied substantially by site. Factors amenable to change that may improve follow-up include good communication of results with patients and providing colposcopy at the site of primary care.

Objectives: We sought to demonstrate the ability that noninvasive in vivo magnetic resonance imaging (MRI) has to quantify the different components within atherosclerotic plaque., Background: Atherosclerotic plaque composition plays a critical role in both lesion stability and subsequent thrombogenicity. Noninvasive MRI is a promising tool for the characterization of plaque composition., Method: Thoracic and abdominal aortic atherosclerotic lesions were induced in rabbits (n = 5). Nine months later, MRI was performed in a 1.5T system. Fast spin-echo sequences (proton density-weighted and T2-weighted [T2W] images) were obtained (in-plane resolution: 350 x 350 microns, slice thickness: 3 mm). Magnetic resonance images were correlated with matched histopathological sections (n = 108)., Results: A significant correlation (p < 0.001) was observed for mean wall thickness and vessel wall area between MRI and histopathology (r = 0.87 and r = 0.85, respectively). The correlation was also present on subanalysis of the thoracic and upper part of the abdominal aorta, susceptible to respiratory motion artifacts. There was a significant correlation for plaque composition (p < 0.05) between MRI and histopathology for the analysis of lipidic (low signal on T2W, r = 0.81) and fibrous (high signal on T2W, r = 0.86) areas with Oil Red O staining. T2-weighted images showed greater contrast than proton density-weighted between these different components of the plaques as assessed by signal intensity ratio analysis with the mean difference in signal ratios of 0.47 (S.E. 0.012, adjusted for clustering of observations within lesions) being significantly different from 0 (t1 = 39.1, p = 0.016)., Conclusions: In vivo noninvasive high resolution MRI accurately quantifies fibrotic and lipidic components of atherosclerosis in this model. This may permit the serial analysis of therapeutic strategies on atherosclerotic plaque stabilization.

Objective: To assess the effect on staff- and patient-related complications of a needleless intermittent intravenous access system with a reflux valve for peripheral infusions., Design: A 6-month cross-over clinical trial (phase I, 13 weeks; phase II, 12 weeks) of a needleless intermittent intravenous access system (NL; study device) compared to a conventional heparin-lock system (CHL, control device) was performed during 1991 on 16 medical and surgical units. A random selection of patients was assessed for local intravenous-site complications; all patients were assessed for the development of nosocomial bacteremia and device-related complications. Staff were assessed for percutaneous injuries and participated in completion of product evaluations. A cost analysis of the study compared to the control device was performed., Setting: A 1,100-bed, teaching, referral medical center. PATIENTS AND STAFF PARTICIPANTS: 594 patients during 602 patient admissions, comprising a random sample of all patients with a study or control device inserted within a previous 24-hour period on study and control units, were assessed for local complications. The 16 units included adult inpatient general medicine, surgical, and subspecialty units. Pediatrics, obstetrics-gynecology, and intensive-care units were excluded. All patients on study and control units were assessed for development of nosocomial bacteremia and device-related complications. All staff who utilized, manipulated, or may have been exposed to sharps on study and control units were assessed for percutaneous injuries. Nursing staff completed product evaluations., Intervention: The study device, a needleless intermittent intravenous access system with a reflux valve, was compared to the control device, a conventional heparin lock, for peripheral infusions., Results: During the study, 35 percutaneous injuries were reported. Eight injuries were CHL-related; no NL-related injuries were reported (P=.007). An evaluation of 602 patient admissions, 1,134 intermittent access devices, and 2,268 observed indwelling device days demonstrated more pain at the insertion site for CHL than NL; however, no differences in objective signs of phlebitis were noted. Of 773 episodes of positive blood cultures on study and control units, 6 (0.8%) were device-related (assessed by blinded investigator), with no difference between NL and CHL. Complications, including difficulty with infusion (P<.001) and disconnection of intravenous tubing from device (P<.001), were reported more frequently with CHL than with NL. Of nursing staff responding to a product evaluation survey, 95.2% preferred the study over control device. The projected annual incremental cost to our institution for hospitalwide implementation of NL for intermittent access for peripheral infusions was estimated at $82,845, or $230 per 1,000 patient days., Conclusions: A needleless intermittent intravenous access system with a reflux valve for peripheral infusions is effective in reducing percutaneous injuries to staff and is not associated with an increase in either insertion-site complications or nosocomial bacteremia. Institutions should consider these data, available institutional resources, and institution-specific data regarding the frequency and risk of intermittent access-device-related injuries and other types of sharps injuries in their staff when selecting the above or other safety devices.

The purpose of this study was to develop a bedside assay based on the in vitro glycolysis of a whole blood sample that could detect primed neutrophils (PMNs). A mathematical index of the PMN response to exogenous stimulation with phorbol myristate 13-acetate (PMA), called the Delta value, was derived by comparing the increase in glycolysis for paired blood samples with and without PMA to that expected from normal subjects. Delta values for systemic inflammatory response syndrome/sepsis patients (9.09 +/- 7.61) (N = 36) were significantly higher than normal controls (2.02 +/- 1.76) (N = 51), nonsepsis ICU patients (3.81 +/- 2.80) (N = 14) and patients in septic shock (2.33 +/- 3.04) (N = 10) (p < .05). Delta values were consistently reflected in parallel measurements of increased reactive oxygen species production by neutrophils detected cytofluorometrically. PMN priming can be simply and rapidly detected by an assay based on the numbers of PMNs and erythrocytes and the measured rates of in vitro glycolysis of paired whole blood samples with and without PMA.

Breast cancer is a leading cause of cancer deaths in women. Although mammography is recognized as the most effective early detection method for breast cancer, it remains underutilized. Communications theory and practice, with its emphasis on formative research, can provide a basis for developing strategies effective in changing mammography-related behaviors. Formative research, an important component of communications planning, can offer information useful in developing suitable messages and materials. The National Cancer Institute conducted small group discussions with white and black women, ages 40 to 75, to explore their attitudes, knowledge, and beliefs about mammography. Findings reinforced the results from quantitative surveys indicating that a perceived lack of their own need for the examination, lack of a physician referral, and procrastination were the main reasons that the women reported for not having mammograms. The discussions provided detailed information about the factors that can be used to guide development of messages and materials to promote mammography use. The results indicate that strategies for messages directed to either black or white women ages 40 years and older need to stress the same key message points. The points are that all women ages 40 and older are at risk for breast cancer; breast cancer can be treated successfully if it is detected early enough; mammography can detect breast cancer before a lump can be felt by a woman or her physician; women need to follow screening guidelines for age and frequency for screening; and mammography is a low-risk, quick, and painless procedure. Communication channels to reach women should include television, newspapers, magazines, and information available in physicians' offices.

A 52-year-old woman presented with ventricular tachycardia after receiving amiodarone for the previous 18 months. The chest roentgenogram revealed evidence of multiple pleural-based cavitary nodules despite the absence of respiratory disease on clinical examination. The nodules were attributed to amiodarone because of histologic changes noted at open-lung biopsy. The cavitating nodules cleared with the discontinuation of amiodarone.