Long-Term Outcome after Prolonged Mechanical Ventilation. A Long-Term Acute-Care Hospital Study.

Rationale: Patients managed at a long-term acute-care hospital (LTACH) for weaning from prolonged mechanical ventilation are at risk for profound muscle weakness and disability. Objectives: To investigate effects of prolonged ventilation on survival, muscle function, and its impact on quality of life at 6 and 12 months after LTACH discharge. Methods: This was a prospective, longitudinal study conducted in 315 patients being weaned from prolonged ventilation at an LTACH. Measurements and Main Results: At discharge, 53.7% of patients were detached from the ventilator and 1-year survival was 66.9%. On enrollment, maximum inspiratory pressure (Pimax) was 41.3 (95% confidence interval, 39.4-43.2) cm H2O (53.1% predicted), whereas handgrip strength was 16.4 (95% confidence interval, 14.4-18.7) kPa (21.5% predicted). At discharge, Pimax did not change, whereas handgrip strength increased by 34.8% (P < 0.001). Between discharge and 6 months, handgrip strength increased 6.2 times more than did Pimax. Between discharge and 6 months, Katz activities-of-daily-living summary score improved by 64.4%; improvement in Katz summary score was related to improvement in handgrip strength (r = -0.51; P < 0.001). By 12 months, physical summary score and mental summary score of 36-item Short-Form Survey returned to preillness values. When asked, 84.7% of survivors indicated willingness to undergo mechanical ventilation again. Conclusions: Among patients receiving prolonged mechanical ventilation at an LTACH, 53.7% were detached from the ventilator at discharge and 1-year survival was 66.9%. Respiratory strength was well maintained, whereas peripheral strength was severely impaired throughout hospitalization. Six months after discharge, improvement in muscle function enabled patients to perform daily activities, and 84.7% indicated willingness to undergo mechanical ventilation again.

Effect of pressure support vs unassisted breathing through a tracheostomy collar on weaning duration in patients requiring prolonged mechanical ventilation: a randomized trial.

IMPORTANCE: Patients requiring prolonged mechanical ventilation (>21 days) are commonly weaned at long-term acute care hospitals (LTACHs). The most effective method of weaning such patients has not been investigated. OBJECTIVE: To compare weaning duration with pressure support vs unassisted breathing through a tracheostomy collar in patients transferred to an LTACH for weaning from prolonged ventilation. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2010, a randomized study was conducted in tracheotomized patients transferred to a single LTACH for weaning from prolonged ventilation. Of 500 patients who underwent a 5-day screening procedure, 316 did not tolerate the procedure and were randomly assigned to receive weaning with pressure support (n = 155) or a tracheostomy collar (n = 161). Survival at 6- and 12-month time points was also determined. MAIN OUTCOME MEASURE: Primary outcome was weaning duration. Secondary outcome was survival at 6 and 12 months after enrollment. RESULTS: Of 316 patients, 4 were withdrawn and not included in analysis. Of 152 patients in the pressure-support group, 68 (44.7%) were weaned; 22 (14.5%) died. Of 160 patients in the tracheostomy collar group, 85 (53.1%) were weaned; 16 (10.0%) died. Median weaning time was shorter with tracheostomy collar use (15 days; interquartile range [IQR], 8-25) than with pressure support (19 days; IQR, 12-31), P = .004. The hazard ratio (HR) for successful weaning rate was higher with tracheostomy collar use than with pressure support (HR, 1.43; 95% CI, 1.03-1.98; P = .033) after adjusting for baseline clinical covariates. Use of the tracheostomy collar achieved faster weaning than did pressure support among patients who did not tolerate the screening procedure between 12 and 120 hours (HR, 3.33; 95% CI, 1.44-7.70; P = .005), whereas weaning time was equivalent with the 2 methods in patients who did not tolerate the screening procedure within 0 to 12 hours. Mortality was equivalent in the pressure-support and tracheostomy collar groups at 6 months (55.92% vs 51.25%; 4.67% difference, 95% CI, -6.4% to 15.7%) and at 12 months (66.45% vs 60.00%; 6.45% difference, 95% CI, -4.2% to 17.1%). CONCLUSION AND RELEVANCE: Among patients requiring prolonged mechanical ventilation and treated at a single long-term care facility, unassisted breathing through a tracheostomy, compared with pressure support, resulted in shorter median weaning time, although weaning mode had no effect on survival at 6 and 12 months. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01541462.

Learner Driver Experience and Teenagers' Crash Risk During the First Year of Independent Driving.

Importance: One mechanism for teenagers' elevated crash risk during independent driving may be inadequate learner driving experience. Objective: To determine how learner driver experience was associated with crash risk during the first year of independent driving. Design, Setting, and Participants: Youth aged 15.5 to 16.1 years at recruitment were eligible to participate. Participants' vehicles were instrumented with sensors, and driving was recorded during the learner period through 1 year of independent driving. Data were collected from January 2011 through August 2014 in southwestern Virginia. Exposures: The amount, consistency and variety of practice, driving errors, and kinematic risky driving (KRD) rates during the learner period were recorded. Surveys, including one on sensation-seeking personality traits, were assessed at baseline. Main Outcomes and Measures: Cox proportional hazard regressions examined associations between individual characteristics and learner driving experience with driving time to first crash and all crashes in the first year of independent driving. So that hazard ratios (HRs) can be directly comparable, units of measurement were standardized to the interquartile range. Results: Of 298 individuals who responded to recruitment, 90 fulfilled the criteria and 82 completed the study (of whom 75 were white [91%] and 44 were girls [54%]). Teenage participants drove a mean (SD) of 1259.2 (939.7) miles over 89 days during the learner period. There were 49 property-damage crashes and/or police-reportable crashes during independent driving. Factors associated with driving time to first crash included higher sensation-seeking personality scale scores (HR, 1.67 [95% CI, 1.08-2.57] per 0.75-unit increase), learner driving KRD rates (HR, 1.27 [95% CI, 1.12-1.43] per 9.24-unit increase), and learner driving errors (HR, 0.44 [95% CI, 0.22-0.86] per increase of 6.48 errors). Similar results were obtained for all crashes in the first year, with the addition of consistency of learner driving practice (HR, 0.61 [95% CI, 0.38-0.99] per 0.23-unit increase). Conclusions and Relevance: Individual characteristics and learner driving experiences were associated with crash risk during independent driving. As expected, there was an association between sensation seeking and crashes. Elevated KRD rates during the learner period may reflect risky driving behavior among novices or tolerance to abrupt maneuvers by parents who supervise driving. Consistent practice throughout the learner period could reduce teenage crash risk, which is supported by learning theories indicating distributed practice is effective for developing expertise. Errors during practice may constitute learning events that reinforce safer driving. Physicians could encourage parents to provide opportunities for regular practice driving and monitor their teenager's KRD rates during the learner period using in-vehicle or smartphone-based technology.

Hypoxemia in patients on chronic opiate therapy with and without sleep apnea.

OBJECTIVE: Animal models have shown a quantal slowing of respiratory pattern when exposed to opioid agonist, in a pattern similar to that observed in central sleep apnea. We postulated that opioid-induced hypoventilation is more likely to be associated with sleep apnea rather than hypoventilation alone. Since we did not have a direct measure of hypoventilation we used hypoxemia as an indirect measure reasoning that significant hypoventilation would not occur in the absence of hypoxemia. METHODS: We conducted a retrospective analysis of 98 consecutive patients on chronic opioid medications who were referred for overnight polysomnography. All patients on chronic opioids seen in the chronic pain clinic were referred for a sleep study regardless of whether they had sleep symptoms or not. Sleep-related hypoxemia was defined as arterial oxyhemoglobin saturation of less than 90% for more than 5 min with a nadir of

Accuracy of autotitrating CPAP to estimate the residual Apnea-Hypopnea Index in patients with obstructive sleep apnea on treatment with autotitrating CPAP.

OBJECTIVE: Autotitrating continuous positive airway pressure (auto-CPAP) devices now have a smart card (a pocket-sized card with embedded integrated circuits which records data from the CPAP machine such as CPAP usage, CPAP pressure, large leak, etc.) which can estimate the Apnea-Hypopnea Index (AHI) on therapy. The aim of this study was to determine the accuracy of auto-CPAP in estimating the residual AHI in patients with obstructive sleep apnea (OSA) who were treated with auto-CPAP without a CPAP titration study. PATIENTS AND METHODS: We studied 99 patients with OSA from April 2005 to May 2007 who underwent a repeat sleep study using auto-CPAP. The estimated AHI from auto-CPAP was compared with the AHI from an overnight polysomnogram (PSG) on auto-CPAP using Bland-Altman plot and likelihood ratio analyses. A PSG AHI cutoff of five events per hour was used to differentiate patients optimally treated with auto-CPAP from those with residual OSA on therapy. RESULTS: Bland and Altman analysis showed good agreement between auto-CPAP AHI and PSG AHI. There was no significant bias when smart card estimates of AHI at home were compared to smart card estimates obtained in the sleep laboratory. An auto-CPAP cutoff for the AHI of six events per hour was shown to be optimal for differentiating patients with and without residual OSA with a sensitivity of 0.92 (95% confidence interval (CI) 0.76 to 0.98) and specificity of 0.90 (95% CI 0.82 to 0.95) with a positive likelihood ratio (LR) of 9.6 (95% CI 5.1 to 21.5) and a negative likelihood ratio of 0.085 (95% CI 0.02 to 0.25). Auto-CPAP AHI of eight events per hour yielded the optimal sensitivity (0.94, 95% CI 0.73 to 0.99) and specificity (0.90, 95% CI 0.82 to 0.95) with a positive LR of 9.6 (95% CI 5.23 to 20.31) and a negative LR of 0.065 (95% CI 0.004 to 0.279) to identify patients with a PSG AHI of > or = 10 events per hour. CONCLUSION: Auto-CPAP estimate of AHI may be used to estimate residual AHI in patients with OSA of varying severity treated with auto-CPAP.

Central sleep apnea induced by acute ingestion of opioids.

OBJECTIVES: Three cases are presented in which patients were using opioids as required for nonmalignant pain management and significant central sleep apnea developed. Patients in the first two cases had no evidence of sleep-related breathing disorders on polysomnography until they ingested an opioid for treatment of chronic pain during the night and severe central sleep apnea developed. The patient in our third case had established obstructive sleep apnea but experienced a significant number of central events after the ingestion of an opioid analgesic, leading to worsening severity of his underlying sleep-related breathing disorder. CONCLUSION: The short-term ingestion of opioid analgesics can precipitate central sleep apnea in patients with chronic pain receiving long-term opiate therapy who otherwise show no evidence of central sleep apnea and have no cardiac or neurologic disease that would predispose them to central sleep apnea.

Sleep-disordered breathing and chronic opioid therapy.

OBJECTIVE: To assess the relation between medications prescribed for chronic pain and sleep apnea. DESIGN: An observational study of chronic pain patients on opioid therapy who received overnight polysomnographies. Generalized linear models determined whether a dose relation exists between methadone, nonmethadone opioids, and benzodiazepines and the indices measuring sleep apnea. SETTING: A private clinic specializing in the treatment of chronic pain. PATIENTS: Polysomnography was sought for all consecutive (392) patients on around-the-clock opioid therapy for at least 6 months with a stable dose for at least 4 weeks. Of these, 147 polysomnographies were completed (189 patients declined, 56 were directed to other sleep laboratories by insurance companies, and data were incomplete for seven patients). Available data were analyzed on 140 patients. OUTCOME MEASURES: The apnea-hypopnea index to assess overall severity of sleep apnea and the central apnea index to assess central sleep apnea. RESULTS: The apnea-hypopnea index was abnormal (> or =5 per hour) in 75% of patients (39% had obstructive sleep apnea, 4% had sleep apnea of indeterminate type, 24% had central sleep apnea, and 8% had both central and obstructive sleep apnea); 25% had no sleep apnea. We found a direct relation between the apnea-hypopnea index and the daily dosage of methadone (P = 0.002) but not to other around-the-clock opioids. We found a direct relation between the central apnea index and the daily dosage of methadone (P = 0.008) and also with benzodiazepines (P = 0.004). CONCLUSIONS: Sleep-disordered breathing was common in chronic pain patients on opioids. The dose-response relation of sleep apnea to methadone and benzodiazepines calls for increased vigilance.

New strains of bacteria and exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: The role of bacterial pathogens in acute exacerbations of chronic obstructive pulmonary disease is controversial. In older studies, the rates of isolation of bacterial pathogens from sputum were the same during acute exacerbations and during stable disease. However, these studies did not differentiate among strains within a bacterial species and therefore could not detect changes in strains over time. We hypothesized that the acquisition of a new strain of a pathogenic bacterial species is associated with exacerbation of chronic obstructive pulmonary disease. METHODS: We conducted a prospective study in which clinical information and sputum samples for culture were collected monthly and during exacerbations from 81 outpatients with chronic obstructive pulmonary disease. Molecular typing of sputum isolates of nonencapsulated Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa was performed. RESULTS: Over a period of 56 months, the 81 patients made a total of 1975 clinic visits, 374 of which were made during exacerbations (mean, 2.1 per patient per year). On the basis of molecular typing, an exacerbation was diagnosed at 33.0 percent of the clinic visits that involved isolation of a new strain of a bacterial pathogen, as compared with 15.4 percent of visits at which no new strain was isolated (P<0.001; relative risk of an exacerbation, 2.15; 95 percent confidence interval, 1.83 to 2.53). Isolation of a new strain of H. influenzae, M. catarrhalis, or S. pneumoniae was associated with a significantly increased risk of an exacerbation. CONCLUSIONS: The association between an exacerbation and the isolation of a new strain of a bacterial pathogen supports the causative role of bacteria in exacerbations of chronic obstructive pulmonary disease.

High-resolution CT findings in patients with pulmonary tuberculosis: correlation with the degree of smear positivity.

BACKGROUND: There are data about the relationship between morphologic findings on high-resolution computed tomography (HRCT) and the number of acid-fast bacilli (AFB) on sputum smears in patients with pulmonary tuberculosis (PTB). It was also shown that existence of cavities and airspace consolidation might be related to smear positivity in PTB patients. However, there is no study suggesting a relationship between AFB on sputum smears and radiologic extent of disease based on HRCT findings. AIM: In this study, we investigated a relationship between the degree of smear positivity and radiologic extent of disease based on HRCT findings and, the degree of smear positivity and different pulmonary parenchymal changes on HRCTs of the PTB patients. METHODS: Sixty-one male patients with PTB (mean age: 22+/-3.2) were included into the study. HRCT images were assessed for patterns, distribution, and profusion of pulmonary abnormalities. Dividing the lungs into 3 zones, profusion of abnormalities was assessed. A profusion score was given. Patients were divided as smear positive and smear negative and compared for the scores of HRCT findings. Smear-positive patients were divided into 4 groups as per grading of the sputum AFB smear: group I (sputum 1+), group II (sputum 2+), group III (sputum 3+), and group IV (sputum 4+). Correlations were investigated between the degree of smear positivity and the scores of HRCT findings. RESULTS: A significant correlation between radiologic extent of the disease based on HRCT and the degree of smear positivity was found (r=0.63, P=0.0001). There were also significant correlations between the degree of smear positivity and the scores of different HRCT findings. Nodule, cavity, and bronchial lesions are the most important contributors of the predictive properties of the total score. There was significant differences for the scores of HRCT findings between smear-positive and smear-negative patients. CONCLUSIONS: Our study suggests that radiologic extent of disease based on HRCT findings in patients with PTB correlated with the degree of smear positivity. Different HRCT findings such as nodule, cavitation, ground-glass opacity, consolidation, and bronchial lesion are significantly associated with smear-positive PTB. Particularly, nodules, cavities, and bronchial lesions might be predictors of smear positivity in patients with PTB. This study also suggests that the thickness of cavity wall and the distance of cavity from central airways might be related to the degree of smear positivity.

A decision aid for COPD patients considering inhaled steroid therapy: development and before and after pilot testing.

BACKGROUND: Decision aids (DA) are tools designed to help patients make specific and deliberative choices among disease management options. DAs can improve the quality of decision-making and reduce decisional conflict. An area not covered by a DA is the decision of a patient with chronic obstructive pulmonary disease (COPD) to use inhaled steroids which requires balancing the benefits and downsides of therapy. METHODS: We developed a DA for COPD patients considering inhaled steroid therapy using the Ottawa Decision Support Framework, the best available evidence for using inhaled steroid in COPD and the expected utility model. The development process involved patients, pulmonologists, DA developers and decision making experts. We pilot tested the DA with 8 COPD patients who completed an evaluation questionnaire, a knowledge scale, and a validated decisional conflict scale. RESULTS: The DA is a computer-based interactive tool incorporating four different decision making models. In the first part, the DA provides information about COPD as a disease, the different treatment options, and the benefits and downsides of using inhaled steroids. In the second part, it coaches the patient in the decision making process through clarifying values and preferences. Patients evaluated 10 out of 13 items of the DA positively and showed significant improvement on both the knowledge scale (p = 0.008) and the decisional conflict scale (p = 0.008). CONCLUSION: We have developed a computer-based interactive DA for COPD patients considering inhaled steroids serving as a model for other DAs in COPD, in particular related to inhaled therapies. Future research should assess the DA effectiveness.

Factors Influencing Learner Permit Duration.

An increasing number of countries are requiring an extended learner permit prior to independent driving. The question of when drivers begin the learner permit period, and how long they hold the permit before advancing to independent licensure has received little research attention. Licensure timing is likely to be related to "push" and "pull" factors which may encourage or inhibit the process. To examine this question, we recruited a sample of 90 novice drivers (49 females and 41 males, average age of 15.6 years) soon after they obtained a learner permit and instrumented their vehicles to collect a range of driving data. Participants completed a series of surveys at recruitment related to factors that may influence licensure timing. Two distinct findings emerged from the time-to-event analysis that tested these push and pull factors in relation to licensure timing. The first can be conceptualized as teens' motivation to drive (push), reflected in a younger age when obtaining a learner permit and extensive pre-permit driving experience. The second finding was teens' perceptions of their parents' knowledge of their activities (pull); a proxy for a parents' attentiveness to their teens' lives. Teens who reported higher levels of their parents' knowledge of their activities took longer to advance to independent driving. These findings suggest time-to-licensure may be related to teens' internal motivation to drive, and the ability of parents to facilitate or impede early licensure.

Simulated obesity-related changes in lung volume increases airway responsiveness in lean, nonasthmatic subjects.

STUDY OBJECTIVE: To determine if obesity-related changes in lung volume might contribute to airway reactivity, we investigated the effects of simulated mild obesity-related lung volume reductions on airway responsiveness in lean, nonasthmatic subjects. PARTICIPANTS AND METHODS: We simulated the lung volume reductions of class 1 obesity in eight lean, nonasthmatic subjects by externally mass loading the chest wall and abdomen, and shifting blood volume into the lung with lower limb compression (LLC). Airway responsiveness was assessed by measuring FEV(1) before and after methacholine challenge tests (1, 2.5, 5, 10, and 25 mg/mL) with the following: (1) no intervention (control); (2) external chest loading (CL); (3) LLC; and (4) CL and LLC (COMB) on separate days. Lung function was measured before and after CL, LLC, and COMB were applied. RESULTS: The application of CL, LLC, and COMB decreased expiratory reserve volume, functional residual capacity, and total lung capacity compared with baseline. FVC and FEV(1) decreased significantly with CL and COMB, while FEV(1)/FVC did not change compared to baseline. The maximal response to the methacholine challenge increased with CL, LLC, and COMB, with a mean maximal fall of FEV(1) of 9%, 11%, and 18%, respectively, compared to a 6% fall with control. CONCLUSIONS: We conclude that decreases in lung volume increase airway responsiveness and may account for the increased propensity for increased airway responsiveness in the obese.

Pulmonary function and abdominal adiposity in the general population.

BACKGROUND: The prevalence of obesity is increasing, and there is evidence that obesity, in particular abdominal obesity as a marker of insulin resistance, is negatively associated with pulmonary function. The mechanism for this association and the best marker of abdominal adiposity in relation to pulmonary function is not known. STUDY OBJECTIVE: We assessed the association between pulmonary function and weight, body mass index (BMI), waist circumference, waist/hip ratio, and abdominal height as markers of adiposity and body fat distribution. We used multiple linear regression to analyze the association of pulmonary function (ie, FEV(1) and FVC) [with maneuvers performed in the sitting position] with overall adiposity markers (ie, weight and BMI) and abdominal adiposity markers, stratified by gender, and adjusted for height, age, race, smoking, and other covariates. SETTING AND PARTICIPANTS: A random sample of individuals (n = 2,153) from the general population living in western New York state, 35 to 79 years of age. RESULTS: In women, abdominal height and waist circumference were negatively associated with FEV(1) percent predicted, while all five adiposity markers were negatively associated with FVC percent predicted. In men, all overall and abdominal adiposity markers were inversely associated with FEV(1) percent predicted and FVC percent predicted. CONCLUSION: These results suggest that abdominal adiposity is a better predictor of pulmonary function than weight or BMI, and investigators should consider it when investigating the determinants of pulmonary function.

Brief report: Internal medicine residents', attendings', and nurses' perceptions of the night float system.

BACKGROUND: Residency training programs use the night float system increasingly to meet the new resident work hour regulations. OBJECTIVE: To assess and compare residents', attendings', and nurses' perceptions of the night float system. DESIGN: A survey study. PARTICIPANTS: One hundred and seven residents, 48 attendings, and 69 nurses in a university-based multicenter internal medicine residency program. MEASUREMENTS: Perceived impact on patient care, resident training, and resident performance. RESULTS: The overall response rate was 75%. In general, more residents than both attendings and nurses had positive opinions regarding the night float system, particularly in relation to patient care. Only a small proportion of residents and attendings thought positively about the night float's impact on training quality (29.9%; 18.2%), daily feedback (23.0%; 9.1%), and end of rotation evaluation (21.8%; 6.1%). Less than half of the nurses had positive perceptions of the night residents' performance in terms of promptness (40.9%), physical availability (38.6%), familiarity with the patients' cases, and management plans (15.9%), communication of management plans to nurses (36.4%), professional respect and trust (43.2%), and teamwork (45.5%). CONCLUSIONS: Residents had more positive perceptions than attendings and nurses. Nurses, in particular, had negative perceptions of resident performance in the setting of the night float system.

Prevalence of positional sleep apnea in patients undergoing polysomnography.

STUDY OBJECTIVES: The primary aim of this study was to determine the prevalence of positional obstructive sleep apnea using a functional definition. Positional sleep apnea was defined as a total apnea-hypopnea index (AHI) > or = 5 with a > 50% reduction in the AHI between the supine and nonsupine postures, and an AHI that normalizes (AHI < 5) in the nonsupine posture. A secondary aim was to determine if positional sleep apnea can be diagnosed accurately during a split-night study. DESIGN: Retrospective chart review. SETTING: Two sleep centers in Buffalo, NY, one a Veterans Affairs Western New York Healthcare System Sleep Center (VAWNY) and the other a freestanding ambulatory center (Associated Sleep Center [ASC]). PATIENTS: Three hundred twenty-six patients from the VAWNY, including 57 patients who underwent a split-night study and 242 patients from the ASC who underwent polysomnography. INTERVENTIONS: None. MEASUREMENTS: Patient characteristics and sleep study results. RESULTS: Positional sleep apnea was seen in 49 of 99 patients (49.5%) with mild sleep apnea (AHI, 5 to 15/h), 14 of 72 patients (19.4%) with moderate sleep apnea (AHI, 15 to 30/h), and 5 of 77 patients (6.5%) with severe sleep apnea (AHI > 30/h). Sufficient sleep (> 15 min) in both postures was not seen in 104 of 269 patients (38.7%) and 80 of 242 overnight studies (33.1%) at the VAWNY and ASC, respectively, and was not seen in 47 of 57 split-night studies (82.5%). The percentage of studies with insufficient sleep in both postures was significantly greater for split-night studies (p < 0.0001). CONCLUSIONS: Positional sleep apnea is common particularly in patients with mild disease. Positional sleep apnea cannot usually be assessed during a split-night study.

Fasting glucose is a risk factor for breast cancer: a prospective study.

There is some evidence that glucose and other factors related to glucose metabolism, such as insulin and insulin-like growth-factors (IGFs) may contribute to breast cancer development. The present study analyzed the hypothesis that serum glucose, insulin levels, and IGF-I pattern are associated with breast cancer using a nested case-control study. Between 1987 and 1992, 10,786 women ages 35-69 were recruited in a prospective study in Italy. Women with history of cancer and on hormone therapy were excluded at baseline. At recruitment, blood samples were collected after a 12-h fast between 7:30 and 9:00 a.m. from all of the study participants. After 5.5 years, 144 breast cancer cases were identified among the participants of the cohort. Four matched controls were chosen for each breast cancer case from members of the cohort who did not develop breast cancer during the follow-up period. In premenopausal women, glucose was associated with breast cancer risk: the age, body mass index, and reproductive variable adjusted relative risk (RR) for the highest quartile of serum glucose versus the lowest was 2.8 [95% confidence interval (CI), 1.2-6.5], and P for trend was 0.02. Insulin showed a weaker association with breast cancer, the adjusted RR of the highest quartile versus the lowest was 1.7 (95% CI, 0.7-4.1), and P for trend was 0.14, whereas the adjusted RR of the highest quartile of IGF-I was 3.1 (95% CI, 1.1-8.6), and P for trend was 0.01. Increased levels of insulin-like growth factor binding protein-3 (IGFBP)-3 were related to breast cancer risk: the adjusted RR for the highest quartile was 2.1 (95% CI, 0.95-4.75), and P for trend was 0.02. In postmenopausal women, the associations of glucose, insulin, and IGF-1 pattern were associated with breast cancer risk in heavier subjects characterized by a body mass index higher than 26. These results indicate that chronic alteration of glucose metabolism is related to breast cancer development.

Association between plasma endothelin-1 levels and Cheyne-Stokes respiration in patients with congestive heart failure.

STUDY OBJECTIVES: Elevated plasma endothelin-1 (ET-1) levels have been reported in association with hypoxia and congestive heart failure (CHF). Furthermore, Cheyne-Stokes respiration-central sleep apnea (CSR-CSA) has been found to correlate with the degree of pulmonary hypertension and the severity of CHF; however, the association between ET-1 levels and CSR-CSA has not been investigated previously. SETTING: Veterans Affairs Medical Center. INTERVENTIONS: We studied 46 consecutive patients with CHF (left ventricular function < or = 40%) who underwent right-heart catheterization and overnight polysomnography. Thirty-nine patients completed the study. Sixteen patients (41%) had CSR-CSA, 5 patients (13%) had obstructive apnea, and 18 patients (46%) had no sleep-disordered breathing. Circulating plasma ET-1 levels were assayed in patients with CSR-CSA and in patients with no sleep-disordered breathing using commercially available enzyme-linked immunosorbent assay kits. RESULTS: ET-1 levels were significantly elevated in patients with CSR-CSA (mean +/- SD, 5.4 +/- 1.3 pg/mL) compared to those without central apnea (3.9 +/- 1.1 pg/mL; p < 0.01), and correlated with mean pulmonary artery pressure (r = 0.66, p < 0.01), pulmonary capillary wedge pressure (r = 0.56, p < 0.03), and central apnea frequency (r = 0.66, p < 0.01). In multivariate analysis, the severity of CSR-CSA was the only variable independently associated with plasma ET-1. CONCLUSIONS: We conclude that elevated plasma ET-1 levels are linked to the severity of CSR-CSA. Whether ET-1 represents an important pathogenic factor in CSR-CSA or marker of its occurrence requires further evaluation.

Adhesion molecules in patients with coronary artery disease and moderate-to-severe obstructive sleep apnea.

STUDY OBJECTIVES: It has been suggested that obstructive sleep apnea (OSA)-induced hypoxic stress might contribute to cardiovascular disorders by promoting expression of soluble adhesion molecules. The reported increase of circulating adhesion molecules in patients with OSA remains controversial because confounders such as cardiovascular risk factors and left ventricular function have not been adequately controlled for. We hypothesized that soluble intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, L-selectin, and E-selectin levels are correlated with OSA independent of coexisting coronary artery disease (CAD). SETTINGS: University-affiliated teaching hospitals. DESIGN AND PARTICIPANTS: A prospective study of 61 consecutive subjects with angiographically proven CAD deemed to have stable angina. INTERVENTIONS: Fifteen patients (mean +/- SD) 61.2 +/- 1.9 years old with moderate-to-severe OSA (apnea-hypopnea index [AHI] > or = 20/h) were matched to a control group (AHI < or = 5/h) for age, gender, body mass index, and severity of CAD. Venous blood samples were collected the morning of the sleep study and assayed for human ICAM-1, VCAM-1, L-selectin, and E-selectin with commercially available enzyme-linked immunosorbent assay kits. RESULTS: All but L-selectin were significantly increased in the OSA group compared to the control subjects (ICAM-1, 367.4 +/- 85.2 ng/mL vs 252.8 +/- 68.4 ng/mL, p = 0.008; VCAM-1, 961.5 +/- 281.7 ng/mL vs 639.1 +/- 294.4 ng/mL, p = 0.004; E-selectin, 81.0 +/- 30.4 ng/mL vs 58.1 +/- 23.2 ng/mL, p = 0.03, respectively). The increased levels of adhesion molecules correlated with the AHI and the oxygen desaturation index but not with the severity of hypoxemia or the frequency of arousals. CONCLUSIONS: These findings suggest that OSA modulates the expression of proinflammatory mediators. Further studies should evaluate the influence of adhesion molecules on cardiovascular outcome in CAD patients with OSA.