Adhesion molecule increases in sleep apnea: beneficial effect of positive airway pressure and moderation by obesity.

BACKGROUND: Elevated levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) may contribute to cardiovascular disease and are associated with obstructive sleep apnea (OSA) and obesity. The relationship between OSA and obesity in determining ICAM-1 and VCAM-1 levels, and the effect of treatment, is unclear. OBJECTIVE: Our aim was to study whether positive airway pressure (PAP) usage resulted in changes in ICAM-1 and VCAM-1 after 2 years within 309 OSA patients from the Icelandic Sleep Apnea Cohort, and determine how obesity affected such changes. SUBJECTS/METHODS: The mean body mass index (BMI) was 32.4±5.1 kg m(-2); subjects had moderate-to-severe OSA (apnea-hypopnea index=45.0±20.2) and 79% were male. There were 177 full PAP users (⩾4 h per night and ⩾20 of last 28 nights), 44 partial (<4 h per night or <20 nights) and 88 nonusers. RESULTS: ICAM-1 (P<0.001) and VCAM-1 (P=0.012) change was significantly different among the PAP groups. The largest ICAM-1 differences were among the most obese subjects (P<0.001). At follow-up, nonusers had increased ICAM-1 compared with decreased levels in full users. All groups had increased VCAM-1, but nonusers had a significantly larger increase than full users. CONCLUSIONS: Within moderate-to-severe OSA patients, PAP usage prevents increases in adhesion molecules observed in nonusers after 2 years. For ICAM-1, the largest effect is in the most obese subjects. As OSA and obesity commonly coexist, the usage of PAP to limit increases in adhesion molecules may decrease the rate of progression of OSA-related cardiovascular disease.

The role of obesity, different fat compartments and sleep apnea severity in circulating leptin levels: the Icelandic Sleep Apnea Cohort study.

OBJECTIVES: To assess whether sleep apnea severity has an independent relationship with leptin levels in blood after adjusting for different measures of obesity and whether the relationship between obstructive sleep apnea (OSA) severity and leptin levels differs depending on obesity level. METHODS: Cross-sectional study of 452 untreated OSA patients (377 males and 75 females), in the Icelandic Sleep Apnea Cohort (ISAC), age 54.3±10.6 (mean±s.d.), body mass index (BMI) 32.7±5.3 kg m(-2) and apnea-hypopnea index 40.2±16.1 events per h. A sleep study and magnetic resonance imaging of abdominal visceral and subcutaneous fat volume were performed, as well as fasting serum morning leptin levels were measured. RESULTS: Leptin levels were more highly correlated with BMI, total abdominal and subcutaneous fat volume than visceral fat volume per se. No relationship was found between sleep apnea severity and leptin levels, assessed within three BMI groups (BMI <30, BMI 30-35 and BMI > or =35 kg m(-2)). In a multiple linear regression model, adjusted for gender, BMI explained 38.7% of the variance in leptin levels, gender explained 21.2% but OSA severity did not have a significant role and no interaction was found between OSA severity and BMI on leptin levels. However, hypertension had a significant effect on the interaction between OSA severity and obesity (P=0.04). In post-hoc analysis for nonhypertensive OSA subjects (n=249), the association between leptin levels and OSA severity explained a minor but significant variance (3.2%) in leptin levels. This relationship was greatest for nonobese nonhypertensive subjects (significant interaction with obesity level). No relationship of OSA severity and leptin levels was found for hypertensive subjects (n=199). CONCLUSION: Obesity and gender are the dominant determinants of leptin levels. OSA severity is not related to leptin levels except to a minor degree in nonhypertensive nonobese OSA subjects.

Identification of craniofacial risk factors for obstructive sleep apnoea using three-dimensional MRI.

The alteration of craniofacial structures has been associated with obstructive sleep apnoea (OSA). We hypothesised that: 1) a smaller mandible is a risk factor for OSA; and 2) the previously observed inferiorly positioned hyoid bone in apnoeics is associated with enlarged tongue volume. This is a case-control study using three-dimensional magnetic resonance imaging cephalometry. 55 apneics and 55 controls were matched for age, sex and race. The analysis was stratified by sex and controlled for age, race, height, neck visceral fat, skeletal type and tongue volume. We found that a 1-sd increase in mandibular length and depth were associated with decreased risk of sleep apnoea (OR 0.52, 95% CI 0.28-0.99 and OR 0.46, 95% CI 0.23-0.91, respectively) in males but not in females. Greater hyoid-to-nasion (OR 2.64, 95% CI 1.19-5.89 in males and OR 5.01, 95% CI 2.00-12.52 in females) and supramentale-to-hyoid (OR 2.39, 95% CI 1.12-5.14) in males and OR 3.38, 95% CI 1.49-7.68 in females) distances were associated with increased risk of OSA. The difference for hyoid position between apnoeics and controls was lost after controlling for tongue volume. Enlargement of tongue is likely to be the pathogenic factor for inferior-posterior positioning of hyoid. A small and shallow mandible is an independent risk factor for OSA in males but not in females.

Predictors of body size in the first 2 y of life: a high-risk study of human obesity.

OBJECTIVE: To ascertain the predictors of body size at 2 y of age. DESIGN: : Prospective, longitudinal study of risk factors for weight gain of infants at high or low risk of obesity by virtue of their mothers' obesity or leanness. SUBJECTS: A total of 40 infants of obese mothers and 38 infants of lean mothers, equally divided among boys and girls. METHODS: Measurement of dependent variables: weight, length and skinfold thicknesses at 3, 6, 9, 12, 18 and 24 months and percent body fat at 3, 12 and 24 months. Measurement of independent variables: average daily caloric consumption at 3, 6, 9, 12, 18 and 24 months; and, at 3 months, nutritive sucking behavior during a test meal, total energy expenditure (TEE), sleeping energy expenditure (SEE), estimation of nonsleeping energy expenditure (TEE-SEE) and socioeconomic status. Parental weights and heights were obtained by self-report at the time of recruitment. Partial correlation and mixed effects linear regression analyses were performed. RESULTS: Measures of body size (weight, length, skinfold thicknesses) and percent of body fat were almost identical between high- and low-risk groups at all times. Energy intake during six occasions over the 2 y, sucking behavior, family income and TEE predicted weight gain, controlling for body length. Parental body mass index was not associated with the child's body size during the first 2 y. During the first year, there were strong lagged correlations between energy intake and body weight and smaller correlations between protein intake and body weight. CONCLUSION: Energy intake, and not energy expenditure, was the determinant of body size in these infants at 2 y of age, as it had been at 1 y. Sucking behavior and TEE (positively) and family income (negatively) also contributed to body weight at 2 y. The novel finding of a lagged correlation between energy intake and body weight early in life suggests that energy intake is programmed for future growth and development.

An algorithm to stratify sleep apnea risk in a sleep disorders clinic population.

Obstructive sleep apnea may lead to complications if not identified and treated. Polysomnography is the diagnostic standard, but is often inaccessible due to bed shortages. A system that facilitates prioritization of patients requiring sleep studies would thus be useful. We retrospectively compared the accuracy of a two-stage risk-stratification algorithm for sleep apnea using questionnaire plus nocturnal pulse oximetry against using polysomnography to identify patients without apnea (Objective 1) and those with severe apnea (Objective 2). Patients were those referred to a university-based sleep disorders clinic due to suspicion of sleep apnea. Subjects completed a sleep apnea symptom questionnaire, and underwent oximetry and two-night polysomnography. We used bootstrap methodology to maximize sensitivity of our model for Objective 1 and specificity for Objective 2. We calculated sensitivity, specificity, positive and negative predictive values, and rate of misclassification error of the two-stage risk-stratification algorithm for each of our two objectives. The model identified cases of sleep apnea with 95% sensitivity and severe apnea with 97% specificity. It excluded only 8% of patients from sleep studies, but prioritized up to 23% of subjects to receive in-laboratory studies. Among sleep disorders clinic referrals, a two-stage risk-stratification algorithm using questionnaire and nocturnal pulse oximetry excluded few patients from sleep studies, but identified a larger proportion of patients who should receive early testing because of their likelihood of having severe disease.

Magnetic resonance imaging of the upper airway structure of children with obstructive sleep apnea syndrome.

The anatomical relationships between lymphoid, bony, and other tissues affecting the shape of the upper airway in children with obstructive sleep apnea syndrome (OSAS) have not been established. We therefore compared the upper airway structure in 18 young children with OSAS (age 4.8 +/- 2.1 yr; 12 males and 6 females) and an apnea index of 4.3 +/- 3.9, with 18 matched control subjects (age, 4.9 +/- 2.0 yr; 12 males and 6 females). All subjects underwent magnetic resonance imaging under sedation. Axial and sagittal T1- and T2-weighted sequences were obtained. Images were analyzed with image-processing software to obtain linear, area, and volumetric measurements of the upper airway and the tissues comprising the airway. The volume of the upper airway was smaller in subjects with OSAS in comparison with control subjects (1.5 +/- 0.8 versus 2.5 +/- 1.2 cm(3); p < 0.005) and the adenoid and tonsils were larger (9.9 +/- 3.9 and 9.1 +/- 2.9 cm(3) versus 6.4 +/- 2.3 and 5.8 +/- 2.2 cm(3); p < 0.005 and p < 0.0005, respectively). Volumes of the mandible and tongue were similar in both groups; however, the soft palate was larger in subjects with OSAS (3.5 +/- 1.1 versus 2.7 +/- 1.2 cm(3); p < 0.05). We conclude that in children with moderate OSAS, the upper airway is restricted both by the adenoid and tonsils; however, the soft palate is also larger in this group, adding further restriction.

Evaluation of the survival prediction index as a model of risk stratification for clinical research in dogs admitted to intensive care units at four locations.

OBJECTIVE: To prospectively evaluate a survival prediction index (SPI) in dogs admitted to intensive care units (ICU) and to generate and test an improved SPI (ie, SPI2). SAMPLE POPULATION: Medical records of 624 critically ill dogs admitted to an ICU. PROCEDURE: Data were collected from dogs within 24 hours after admission to an ICU. Variables recorded reflected function of vital organ systems, severity of underlying physiologic derangement, and extent of physiologic reserve; outcome was defined as dogs that survived or did not survive until 30 days after admission to the ICU. Probabilities of survival were calculated, using an established model (SPI). We then performed another logistic regression analysis, thereby reestimating the variables to create the new SPI2. Cross-validation of the models obtained was performed by randomly assigning the total sample of 624 dogs into an estimation group of 499 dogs and validation group of 125 dogs. RESULTS: Testing of SPI resulted in an area under the curve (AUC) of 0.723. Testing of SPI2 revealed an AUC of 0.773. A backwards-elimination procedure was used to create a model containing fewer variables, and variables were sequentially eliminated. The AUC for the reduced model of SPI2 was 0.76, indicating little loss in predictive accuracy. CONCLUSIONS AND CLINICAL RELEVANCE: The new SPI2 objectively stratified clinical patients into groups according to severity of disease. This index could provide an important tool for clinical research.

Repeated assessment of the endogenous 24-hour profile of blood pressure under constant routine.

The impact of environmental and behavioral factors on the 24-h profile of blood pressure (BP) has been well established. Various attempts have been made to control these exogenous factors, in order to investigate a possible endogenous circadian variation of BP. Recently, we reported the results of the first environmentally and behaviorally controlled laboratory study with 24-h recordings of BP and heart rate (HR) during maintained wakefulness. In this constant-routine study, a pronounced endogenous circadian rhythm of HR was found, but circadian variation of BP was absent. This result suggested that the circadian rhythm of BP observed in earlier controlled studies, with sleep allowed, was evoked by the sleep-wake cycle as opposed to the endogenous circadian pacemaker. In order to verify our previous finding during maintained wakefulness, we repeated the experiment five times with six normotensive, healthy young subjects. Statistical analyses of the hourly measurements of BP and HR confirmed the replicable presence of an endogenous circadian rhythm of HR, as well as the consistent absence of an endogenous circadian variation of BP. Thus, this study provided additional evidence that the 24-h profile of BP--as observed under normal circumstances--is the sole result of environmental and behavioral factors such as the occurrence of sleep, and has no endogenous circadian component.

Inpatient rehabilitation after stroke: a comparison of lengths of stay and outcomes in the Veterans Affairs and non-Veterans Affairs health care system.

BACKGROUND: Patients have longer lengths of hospital stay (LOS) in VA medical centers than in the general health care system. OBJECTIVE: The objective of this study was to determine whether resource use and outcome differences between VA and non-VA inpatient rehabilitation facilities remain after controlling for patient and medical care delivery differences. DESIGN: This analysis involved 60 VA inpatient rehabilitation units and 467 non-VA rehabilitation hospitals and units. Multivariate adjusted resource use and patient outcome differences were compared across setting within patients grouped by severity of disability at admission through assignment to the Function Related Group (FRG) patient classification system. SUBJECTS: The study included 55,438 stroke patients. MEASURES: Study measures were LOS, functional status at discharge, and community discharge. RESULTS: The VA serves a higher proportion of patients who are single, separated, or divorced; are unemployed or retired as a result of disability, and are not white (P < 0.0001). These traits tended to be associated with longer LOS, lower functional outcomes, and reduced rates of community discharge. After adjusting for these and other differences, depending on FRG, average LOS remained from 30% to 200% longer in the VA centers (P < 0.05); average functional outcomes were significantly higher in 8 and lower in 2 FRGs (P < 0.05); and community discharge rates were lower in 12 FRGs (P < 0.05). CONCLUSIONS: While certain variables accounted for some of the observed differences in resource use and outcomes, differences remained after adjustment. Fewer incentives for cost containment and less support in patients' home environments may be among the most important unmeasured determinants of VA differences.

Breast cancer: education, counseling, and adjustment--a pilot study.

The feasibility of a randomized clinical trial to implement and compare the effectiveness of three components of an intervention for women with breast cancer and their partners was tested. The intervention components, standardized education by videotape (SE), telephone counseling (TC), and education with telephone counseling (SE+TC), were designed with a complementary approach to disease management of breast cancer at each of four phases of the breast cancer experience: diagnostic, postsurgery, adjuvant therapy, and ongoing recovery. A standardized Telephone Counseling Training Manual was developed. A nonprobability sample of 12 patient-partner pairs was accrued. Four pairs were randomly assigned to each of the three intervention components. A set of questionnaires was completed by each patient and partner at baseline and following each intervention for assessment of emotional, physical, and social adjustment, and perceived support. Attrition was minimal and return rate for the completed questionnaires at all five data-collection points was high. Validation of the SE and the TC, one of the objectives, was by data from the preliminary descriptive study (Hoskins, 1990-1994), pretests and posttests for standardized education, audiotapes for each phase-specific telephone counseling session, and evaluation forms for each intervention session. The positive findings included significant changes from pre- to postmeasurement in patients' and partners' scores for the standardized education in each of the four phases. Even with the limited statistical power, the effects were marked, lending support for a full-scale randomized clinical trial, to understand better the relative treatment efficacy and differential benefit of one or some interventions over others.

Physical findings and the risk for obstructive sleep apnea. The importance of oropharyngeal structures.

In this study, we hypothesized that anatomic abnormalities of the oropharynx, particularly narrowing of the airway by the lateral pharyngeal walls, tonsils, and tongue, would be associated with an increased likelihood for obstructive apnea among patients presenting to a sleep disorders center. To test this hypothesis, we used data from a cohort of 420 patients presenting to the Penn Center for Sleep Disorders. Associations between individual variables in the clinical evaluation model and sleep apnea as defined by a respiratory disturbance index greater than or equal to 15 events per hour were characterized by odds ratios (ORs) with 95% confidence intervals (CIs). Multivariable logistic regression was used to simultaneously estimate ORs for multiple variables and to control for other relevant patient characteristics. Results showed that narrowing of the airway by the lateral pharyngeal walls (OR = 2.5; 95% CI, 1.6-3.9) had the highest association with obstructive sleep apnea (OSA) followed by tonsillar enlargement (OR = 2.0; 95% CI, 1.0-3.8), enlargement of the uvula (OR = 1.9; 95% CI, 1.2-2.9), and tongue enlargement (OR = 1.8; 95% CI, 1.0-3.1). Low-lying palate, retrognathia, and overjet were not found to be significantly associated with OSA. Controlling for BMI and neck circumference, only lateral narrowing and enlargement of the tonsils maintained their significant (OR = 2.0 and 2.6, respectively). A subgroup analysis examining differences between male and female subjects showed that no oropharyngeal risk factor achieved significance in women while lateral narrowing was the sole independent risk factor in men. These findings suggest that enlargement of the oropharyngeal soft tissue structures, particularly the lateral pharyngeal walls, is associated with an increased likelihood of OSA among patients presenting to sleep disorders centers.

Comparison of nurse practitioner and family physician relative work values.

PURPOSE: With the enactment of the Balanced Budget Act of 1997, American nurse practitioners were granted direct Medicare reimbursement for Part B services. Payment structures in fee-for-service and managed care systems are physician-based, leading to difficulties in constructing payments for other health care professionals. The purpose of this pilot study was to examine the feasibility of using nurse practitioner data for specifying relative work values in the Medicare Fee Schedule for three office-visit codes. DESIGN: An exploratory survey was designed to establish relative work values using magnitude-estimation scaling. Nurse practitioners (N = 43) responded to a structured questionnaire in a national mail survey. Physician data (N = 46) were obtained from a computerized database from the American Academy of Family Physicians. METHODS: The methods used in this study were the same as the process used by the American Medical Association and the Health Care Financing Administration to establish relative work values in the Medicare Fee Schedule. Respondents established relative work values for three Current Procedural Terminology (CPT) codes for office visits (99203, 99213, 99215) commonly billed in primary care practice. Each CPT code descriptor and associated vignette were compared with reference services germane to the practice of nurse practitioners and family physicians, using magnitude-estimation scaling. To establish relative work values for each code, respondents were asked to consider the time to provide the service and intensity of the work involved for each CPT code. FINDINGS: No significant differences between nurse practitioners and family physicians were found in the three CPT codes for relative work values and intensity. Nurse practitioners estimated significantly (p < .01) higher intraservice (face to face) time with patients than did family physicians, and family physicians estimated significantly (p < .05) higher pre-service time for two codes and significantly (p < .05) higher postservice times for three codes. CONCLUSIONS: Nurse practitioner relative work values did not differ significantly from family physician relative work values. Although the sample sizes were small, the significance of the findings support the need for further research with large data sets and additional CPT codes. Such studies could then be used as a basis for decisions about Medicare payment and public policy.

Nurse practitioner services: content and relative work value.

The resource-based relative value scale is used to quantify work for reimbursement of services in the Medicare Fee Schedule. This pilot study explored use of the resource-based relative value scale for services provided by nurse practitioners. Estimation of relative work values for office visits by nurse practitioners was consistent with the Medicare Fee Schedule. Content analysis revealed that nurse practitioners provide additional services including comprehensive patient evaluation and education and attendance to social factors. Future research is needed to examine systems that identify and reimburse nurse practitioners for their services.

A functional strategy for classifying patients after traumatic spinal cord injury.

OBJECTIVES: To present a function-based strategy for classifying patients by expected functional outcomes measured as patients' performances at discharge on each of the 18 component items of the FIMtrade mark instrument (previously known as the Functional Independence Measure). METHODS: Data included records from 3604 inpatients with traumatic spinal cord injury discharged from 358 rehabilitation units or hospitals in 1995. The function-based strategy assigned patients to four Discharge Motor-FIM-Function Related Groups defined by patients' admission performance on the motor-FIM items. RESULTS: The majority of patients whose motor-FIM scores at admission were above 30 were able to groom, dress the upper body, manage bladder function, use a wheelchair, and transfer from bed to chair, either independently or with supervision, by the time of discharge from inpatient rehabilitation. Most patients whose scores were above 52 attained independence in all but the most difficult FIM tasks, such as bathing, tub transfers, and stair climbing. CONCLUSIONS: This classification scheme can be used to determine the degree to which patients' actual FIM outcomes compare to other individuals who had similar levels of disabilities at the time of admission to rehabilitation. The clinician can apply these 'FIM item attainment benchmarks' retrospectively in quality improvement, in guideline development, and in anticipating the types of post-discharge care required by clinically similar groups.

Initiation of physical restraint in nursing home residents following restraint reduction efforts.

In this pilot study a one group pretest posttest design was employed to identify resident characteristics and environmental factors associated with initiation of physical restraint. Predictors of restraint initiation for older adults were examined using secondary analysis of an existing data set of nursing home residents who were subjected to a federal mandate and significant restraint reduction efforts. Lower cognitive status (OR = 1.5 [for every 7-point decrease in Mini-Mental State Examination], 95% CI = 1.0, 2.1) and a higher ratio of licensed nursing personnel (OR = 3.7, 95% CI = 1.2, 11.9) were predictive of restraint initiation. Key findings suggest that restraint initiation occurs, despite significant restraint reduction efforts, when a nursing home resident is cognitively impaired or when more licensed nursing personnel (predominantly licensed practical nurses) are available for resident care. Achievement of restraint-free care in nursing homes requires specific and individualized approaches for residents who are cognitively impaired, as well as greater attention to staff mix of registered nurses, licensed practical nurses, and nursing aides.

Quantitative evaluation of the upper airway during nasopharyngoscopy with the Müller maneuver.

OBJECTIVE: To quantitatively examine changes in the upper airway caliber of normal subjects at graded negative inspiratory pressures generated during nasopharyngoscopy with a Müller maneuver. STUDY DESIGN: Eighteen normal subjects prospectively underwent nasopharyngoscopy with Müller maneuvers. Subjects performed graded and maximal effort Müller maneuvers while sitting upright, and maximal-effort Müller maneuvers in the supine position. Two regions of the upper airway--the retropalatal and retroglossal--were examined. METHODS: Images from the endoscopic examination were objectively analyzed by adjusting manually traced airway contours using full-width, half-maximum edge detection algorithm software. The adjusted tracings' area and dimensions through the airway centroid were measured. RESULTS: Müller maneuvers performed at -40 cm H2O resulted in a 64%+/-17% (P = .0001) reduction in upper airway area that consisted of a 51%+/-20% (P = .0001) reduction in the lateral dimension and a 21%+/-24% (P = .0026) reduction in antero-posterior dimension. Müller maneuvers in the retroglossal region did not significantly reduce airway area (P = .575), but demonstrated an altered airway conformation that consisted of lateral narrowing and an increase in antero-posterior dimension. Changes in body position did not result in significant differences in either airway caliber or airway dimension. CONCLUSIONS: Airway caliber during forced inspiration is mediated primarily through changes in the lateral pharyngeal walls. This study has also shown that antero-posterior and lateral airway structures are largely independent in their response to Müller maneuvers. Similarly, the retropalatal and retroglossal regions of the upper airway respond differently to forced negative intraluminal pressure.

Vasodilator therapy for primary pulmonary hypertension in children.

BACKGROUND: This report presents 13 years of experience with vasodilator therapy for primary pulmonary hypertension (PPH) in children. Two eras were involved: between 1982 and 1987, oral calcium channel blockers were the only agents available for long-term therapy; after 1987, prostacyclin (PGI2) has been available for long-term intravenous use. METHODS AND RESULTS: Seventy-four children underwent short-term vasodilator testing with intravenous PGI2. Those who manifested pulmonary vasodilation ("acute responders") were treated with oral calcium channel blockers. Until 1987, "acute nonresponders" were treated in the same way as long as they had no serious side effects. When PGI2 became available for long-term administration, all nonresponders, as well as those who failed to improve clinically and hemodynamically on calcium channel blockers, were treated with long-term PGI2. In the 31 responders, calcium channel blockers improved survival compared with the 43 nonresponders (P=0.0002). Survival was also better in 24 PGI2-treated nonresponders compared with 22 nonresponders for whom PGI2 was unavailable (P=0.0005) as well as in all children who failed conventional therapy (n=31; P=0.002). CONCLUSIONS: Long-term vasodilator therapy improves survival in children with PPH. In acute responders, oral calcium channel blockers generally suffice. In both nonresponders to short-term testing and responders who fail to improve on calcium channel blockers, continuous intravenous infusion of PGI2 improves survival.