Plasma receptor for advanced glycation end products and clinical outcomes in acute lung injury.

OBJECTIVES: To determine whether baseline plasma levels of the receptor for advanced glycation end products (RAGE), a novel marker of alveolar type I cell injury, are associated with the severity and outcomes of acute lung injury, and whether plasma RAGE levels are affected by lower tidal volume ventilation. DESIGN, SETTING AND PARTICIPANTS: Measurement of plasma RAGE levels from 676 subjects enrolled in a large randomised controlled trial of lower tidal volume ventilation in acute lung injury. MEASUREMENTS AND MAIN RESULTS: Higher baseline plasma RAGE was associated with increased severity of lung injury. In addition, higher baseline RAGE was associated with increased mortality (OR for death 1.38 (95% CI 1.13 to 1.68) per 1 log increment in RAGE; p = 0.002) and fewer ventilator free and organ failure free days in patients randomised to higher tidal volumes. These associations persisted in multivariable models that adjusted for age, gender, severity of illness and the presence of sepsis or trauma. Plasma RAGE was not associated with outcomes in the lower tidal volume group (p = 0.09 for interaction in unadjusted analysis). In both tidal volume groups, plasma RAGE levels declined over the first 3 days; however, the decline was 15% greater in the lower tidal volume group (p = 0.02; 95% CI 2.4% to 25.0%). CONCLUSIONS: Baseline plasma RAGE levels are strongly associated with clinical outcomes in patients with acute lung injury ventilated with higher tidal volumes. Lower tidal volume ventilation may be beneficial in part by decreasing injury to the alveolar epithelium.

Access to health care. Part 3: Older adults.

OBJECTIVES: This report examines access to health care for older adults, 65 years of age and over. In the United States for 1993. Access indicators include having a regular source of care, place of care, main reason for no regular source of care, unmet health care needs, and use of clinical and preventive services. Sociodemographic characteristics include sex, age, race, income, health status, and health insurance coverage. METHODS: Data are from the 1993 Access to Care, Health insurance, and Year 2000 Surveys of the National Health interview Survey (NHIS), a continuing household survey of the civilian noninstitutionalized population of the United States. The sample for the Access to Care and Health insurance surveys contained 61,287 persons in 24,071 households. The sample for the Year 2000 survey was 21,028 persons. RESULTS: Persons with Medicare and private or Medicare and public coverage were more likely to have a regular source of medical care than elderly persons with Medicare only. Over 3.3 million elderly persons had at least one unmet need in 1993. Older adults on Medicare and public or Medicare only coverage were twice as likely to have unmet medical needs than those with Medicare and private coverage. Persons with Medicare and private coverage were more likely to receive immunizations than elderly persons with Medicare and public coverage or Medicare only. CONCLUSIONS: Although the majority of older adults have Medicare, this only provides a basic level of access to the health care system. Older adults who do not supplement Medicare with private coverage are at the greatest risk of having unmet health care needs.

Access to health care. Part 1: Children.

OBJECTIVES: This report presents national estimates of access to medical care and unmet health care needs for children through 17 years of age by selected sociodemographic variables including sex, age, race and/or ethnicity, family income, family structure, place of residence, and health status. In addition, the impact of children's health insurance status on access to care is described. METHODS: Data from the 1993 Access to Care and Health Insurance questionnaires of the National Health Interview Survey (NHIS) are analyzed to examine access indicators. The NHIS is a continuing household survey of the civilian noninstitutionalized population of the United States. The sample included 16,907 children from infants through 17 years of age from 24,071 households. RESULTS: In 1993, over 7.3 million U.S. children had at least one unmet health care need or had medical care delayed because of worry about the cost of care. These health care needs included medical care, dental care, prescription medicine, glasses, and mental health care. In addition, almost 4.2 million children lacked a regular source of health care. Factors related to access indicators included health insurance, family income, race and/or ethnicity, family structure, and place of residence. The lack of health insurance or inability to afford care was the main reason given by respondents for children lacking a regular source of medical care. CONCLUSIONS: In the United States, millions of children do not receive needed health care services. Uninsured children and those in families with low income are at the greatest risk of having unmet health needs.

Access to health care. Part 2: Working-age adults.

OBJECTIVES: This report presents data on access to health care for U.S. working-age adults, 18-64 years old. Access indicators are examined by selected sociodemographic characteristics including sex, age, race and/or ethnicity, place of residence, employment status, income, health status, and health insurance status. METHODS: Data are from the 1993 Access to Care and 1993 Health Insurance Surveys of the National Health Interview Survey (NHIS), a continuing household survey of the civilian noninstitutionalized population of the United States. The sample contained 61,287 persons in 24,071 households. RESULTS: In 1993, approximately 3 out of 4 working-age adults had a regular source of medical care. Nine out of 10 adults with health insurance had a regular source of care compared with 6 out of 10 adults without health insurance. For adults with a regular source of care, 86 percent received care in a private doctor's office, 9 percent in a clinic, and 2 percent in a hospital emergency room. The two main reasons given for not having a regular source of care were "do not need a doctor" (49 percent), and "no insurance can't afford it" (22 percent). Persons in the highest income group were more likely to report no need for a doctor (59 percent) than persons in the lowest income group (35 percent). About 40 percent of uninsured persons and 16 percent of insured persons reported an unmet medical need. CONCLUSIONS: Health insurance plays a key role in the access to medical care services. Persons who are uninsured or have low incomes are at the greatest risk of having unmet medical needs.

The effects of acute hypoxia and hypercapnia on pulmonary mechanics in normal subjects and patients with chronic pulmonary disease.

The influence of progressive hypoxia and hypercapnia on respiratory mechanics was evaluated in 26 subjects (six normal subjects, seven asthmatic subjects, seven patients with IPD, and six patients with COPD). During separate rebreathing runs of progressive isocapnic hypoxia and normoxic hypercapnia, breath-to-breath changes in RL and Cdyn were determined. In five of the six normal subjects, seven of the seven asthmatic subjects, and six of the seven subjects with IPD, RL decreased with both progressive hypoxia and hypercapnia without a change in Cdyn. In the patients with COPD, the effects of hypoxia and hypercapnia on RL and Cdyn were variable. Compared to normal subjects, the changes in RL during hypoxia and hypercapnia were not significantly different in the asthmatic subjects and the patients with IPD. These data provide evidence that acute progressive hypoxia and hypercapnia are associated with significant changes in Raw in both normal subjects and patients with chronic pulmonary disease.

Pneumothorax with Pneumocystis carinii pneumonia in AIDS. Incidence and clinical characteristics.

A retrospective review of the charts of patients with the acquired immunodeficiency syndrome (AIDS) was performed at three university-affiliated teaching hospitals in Denver between May 1982 and April 1987. Patients were evaluated for the presence or absence of Pneumocystis carinii pneumonia (PCP) and for the occurrence of pneumothorax at any time during their clinical course. The incidence of pneumothorax in AIDS patients with PCP was 9.0 percent (8/89), compared with 0 percent (0/45) in AIDS patients without PCP (p less than 0.03). All of the pneumothoraces resolved, most without chest tube placement. This study suggests that in patients with AIDS, PCP is associated with an increased incidence of pneumothorax, while AIDS patients without PCP are not at increased risk for the development of pneumothorax.

Clinicians' approaches to mechanical ventilation in acute lung injury and ARDS.

STUDY OBJECTIVES: To examine clinicians' approaches to mechanical ventilation in patients with acute lung injury (ALI; PaO(2)/fraction of inspired oxygen [FIO(2)] 35 cm H(2)O in 26% of patients. Seventy-eight percent of patients with ARDS received

Total enteral nutrition versus total parenteral nutrition after major torso injury: attenuation of hepatic protein reprioritization.

Reprioritization of hepatic protein synthesis, a process involving accelerated production of acute-phase proteins at the expense of constitutive proteins, accompanies major trauma. The impact of isocaloric, isonitrogenous total enteral nutrition (TEN) versus total parenteral nutrition (TPN) on hepatic reprioritization was investigated in a prospective, randomized trial. Of the 59 patients with an abdominal trauma index (ATI) greater than 15 but not more than 40, 45 evaluable patients were followed. Results from 36 (18 TEN, 18 TPN) evaluable patients revealed that mean serum levels of acute-phase proteins increased, whereas mean serum levels increased to a greater extent in the TPN group. The maximal increase from baseline for the acute-phase response in both groups occurred at postinjury day 5 and was significantly higher for alpha 1-antitrypsin (alpha 1AT, p = 0.03) and orosomucoid (p = 0.02) in the TPN group. Nonacute-phase proteins reached a nadir at day 10 in the TPN group and increased in the TEN group; significant differences between TEN and TPN groups appeared for albumin (p = 0.004) and retinol-binding protein (RBP, p = 0.03); alpha 2-macroglobulin (alpha 2M) approached significance at day 10 (p = 0.07). When change from baseline values was compared, day 10 increases in alpha 2M were significantly higher (p = 0.04) in the TEN group. These data suggest that postinjury TEN attenuates reprioritization of hepatic protein synthesis in patients sustaining major trauma.

Mediators and mechanisms of acute lung injury.

Since last reviewed in this forum, there have been remarkable advances in our understanding of the acute inflammatory process and how it contributes to the development of ALI. As stated in the beginning of this article, it is not possible to even begin to review all the specific advances that have been made. Instead, the author has focused on concepts that have emerged and improved our ability to study the pathogenesis of ARDS. These include the recognition that patients at risk for and with ARDS represent a heterogeneous population, that mediators or markers of inflammation cannot be considered in isolation, that a balance between proinflammatory mediators and inflammatory modulators may be important, and that there are several genetic factors that could contribute to the susceptibility for the development of ARDS. Hopefully these concepts can be expanded and clarified so that the next review of this topic can report on successful therapeutic interventions for the prevention and the treatment of ARDS.

Respiratory failure as a result of drugs, overdoses, and poisonings.

When taking care of critically ill patients, it is paramount to consider all factors that could be contributing to their illness. Even in this brief discussion, it is clear that numerous drugs, procedures, and ingestants are associated with acute respiratory failure from a variety of mechanisms and that a review of all possible drug/poison exposures needs to be done for every patient.

Early detection and markers of sepsis.

In vitro and animal models of sepsis have provided a template for studies of the pathogenesis of sepsis in patients at risk for and with the syndrome. Numerous potential markers have been identified in these models and then looked for in patients. No single marker or combination of markers convincingly identifies sepsis, predicts the development of sepsis, predicts the development of complications of sepsis, or predicts mortality. As discussed, the clinical studies have been complicated by many confounding variables, including the lack of adherence to rigorous definitions, differences in assay methods, differences in timing of the studies, and differences in outcome variables analyzed. In spite of the limitations, the studies have been critical in helping determine the pathogenesis of sepsis in humans. As new mediators and modulators of inflammation are identified, it will be important to study their role as markers, individually and in combination, in human disease.

Income, social stratification, class, and private health insurance: a study of the Baltimore metropolitan area.

Most studies of inequalities and access to health care have used income as the sole indicator of social stratification. Despite the significance of social theory in health insurance research, there are no empirical studies comparing the ability of different models of social stratification to predict health insurance coverage. The aim of this study is to provide a comparative analysis using a variety of theory-driven indicators of social stratification and assess the relative strength of the association between these indicators and private health insurance. Data were collected in a 1993 telephone interview of a random digit dialing sample of the white population in the Baltimore Metropolitan Statistical Area. Indicators of social stratification included employment status, full-time work, education, occupation, industry, household income, firm size, and three types of assets: ownership, organizational, and skill/credential. The association between social stratification and private health insurance was strongest for those having higher household incomes, having attained at least a bachelor's degree, and working in a firm with more than 50 employees, followed by being an owner or manager, and by being employed. The addition of education and firm size improved the prediction of the household income model. The authors conclude that studies of inequalities in health insurance coverage can benefit from the inclusion of theory-driven indicators of social stratification such as human capital, labor market segmentation, and control over productive assets.

The terminal complement complex (sC5b-9) is not specifically associated with the development of the adult respiratory distress syndrome.

Previous investigators suggested that increased plasma levels of the terminal complement complex (sC5b-9) are an early marker for the development of adult respiratory distress syndrome (ARDS) in septic patients. We asked whether an increase in sC5b-9 was also associated with the development of ARDS from other etiologies and whether sC5b-9 measurements consistently reflected complement activation in vivo. We evaluated 75 patients with sepsis, trauma, hypertransfusion, multiple fractures, aspiration, or pancreatitis who were at risk for ARDS but did not develop the syndrome and 23 patients with similar histories who did develop ARDS. Of the latter patients, seven were identified and studied both when they were at risk and when they had ARDS. Serial blood samples were obtained and analyzed for the complement activation products Bb, Ba, C4d, C3d, IC3b, and sC5b-9. All but one of the patients studied had levels of one or more complement fragments that were greater than 2 SD above the mean obtained from 18 normal subjects. In contrast to the report referred to previously, none of the fragments measured, including sC5b-9, was a specific indicator of ARDS, and no combination of complement fragments predicted which patients at risk would develop ARDS. Patients demonstrated evidence of activation of the classical pathway only, alternative pathway only, or both pathways, but none of these was associated with greater risk or severity of disease. In addition, in several patients only late components were activated, suggesting that enzymes other than those derived from complement activation may be responsible. In conclusion, complement can be activated by a variety of mechanisms in critically ill patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The economic impact of injuries: a major source of medical costs.

Data from the 1980 National Medical Care Utilization and Expenditure Survey were analyzed to place the costs for injuries in the context of all medical costs and to describe the distribution by demographic and diagnostic groups. For the non-institutionalized population, injuries, which include intentional and unintentional, were the second leading cause of direct medical costs, accounting for $16,745 million in medical care expenditures and a major contributor to work loss and disability in the US. For the working-age population (17-64 years) injuries were the leading cost category ($11,341 million) and the third most costly category for persons 65 years of age and over ($3,479 million). The preponderance of costs were attributable to hospital-based care. Direct medical costs were disproportionately greater for males, White and other persons, and for those with household incomes less than $5,000. Injury morbidity also accounts for major indirect costs. Fractures accounted for the highest direct medical costs, greatest per capita charges (based on those with charges), and largest number of restricted activity days. These national estimates document the economic importance of injuries and direct public attention to policy imperatives related to research and prevention.

Futile care: prevention and process: educating patients about advance directives is crucial.

The current health care reform movement offers unique opportunities to address the issue of futile care. Possible solutions include the widespread use of advance directives, particularly durable power of attorney and cardiopulmonary resuscitation directives; the establishment of regional consortia for developing guidelines for the reasonable termination of care; and the use of patient registries and structured outcome studies to identify patients for whom treatment is likely to be futile. In addition to developing guidelines, regional consortia can serve as monitors for insurers or managed care plans that may attempt to limit care inappropriately.

The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults.

OBJECTIVE: To determine the effect of a history of chronic alcohol abuse on the incidence of acute respiratory distress syndrome (ARDS) and in-hospital mortality. DESIGN: Prospective cohort study. PATIENTS: A total of 351 medical and surgical intensive care unit patients with one of seven at-risk diagnoses for the development of ARDS. MAIN OUTCOME MEASURES: The development of ARDS and in-hospital mortality. RESULTS: Of the 351 patients enrolled in the study, the incidence of ARDS in patients with a history of alcohol abuse was significantly higher than in patients without a history of alcohol abuse (43% vs 22%) (P < .001; relative risk [RR], 1.98; 95% confidence interval [Cl], 1.32 to 2.85). In patients with sepsis, ARDS developed in 52% of the patients with a prior history of alcohol abuse compared with only 20% in patients without a history of alcohol abuse (P < .001; RR, 2.59; 95% Cl, 1.29 to 5.12). Fifty-one percent (52/102) of the patients who developed ARDS died compared with only 14% (36/249) of patients who did not develop ARDS (P < .001). In the subset of patients who developed ARDS, the in-hospital mortality rate was 65% in patients with a prior history of alcohol abuse. This mortality rate was significantly higher (P = .003) than the mortality rate in patients without a history of alcohol abuse (36%). CONCLUSIONS: A prior history of chronic alcohol abuse significantly increases the risk of developing ARDS in critically ill patients with an identified at-risk diagnosis. Our results may be useful in the earlier and more accurate identification of patients at high risk for developing ARDS.