Treatment of death in the analysis of longitudinal studies of gerontological outcomes.

BACKGROUND: Longitudinal studies in gerontology are characterized by termination of measurement from death. Death is related to many important gerontological outcomes, such as functional disability, and may, over time, change the composition of an older study population. For these reasons, treating death as noninformative censoring of a longitudinal outcome may result in biased estimates of regression coefficients related to that outcome. METHODS: In a longitudinal study of community-living older persons, we analytically and graphically illustrate the dependence between death and functional disability. Relative to survivors, decedents display a rapid decline of functional ability in the months preceding death. Death's strong relationship with functional disability demonstrates that death is not independent of this outcome and, hence, leads to informative censoring. We also demonstrate the "healthy survivor effect" that results from death's selection effect, with respect to functional disability, on the longitudinal makeup of an older study population. RESULTS: We briefly survey commonly used approaches for longitudinal modeling of gerontological outcomes, with special emphasis on their treatment of death. Most common methods treat death as noninformative censoring. However, joint modeling methods are described that take into account any dependency between death and a longitudinal outcome. CONCLUSIONS: In longitudinal studies of older persons, death is often related to gerontological outcomes and, therefore, cannot be safely assumed to represent noninformative censoring. Such analyzes must account for the dependence between outcomes and death as well as the changing nature of the cohort.

Viral ecology of organic and inorganic particles in aquatic systems: avenues for further research.

Viral abundance and processes in the water column and sediments are well studied for some systems; however, we know relatively little about virus-host interactions on particles and how particles influence these interactions. Here we review virus-prokaryote interactions on inorganic and organic particles in the water column. Profiting from recent methodological progress, we show that confocal laser scanning microscopy in combination with lectin and nucleic acid staining is one of the most powerful methods to visualize the distribution of viruses and their hosts on particles such as organic aggregates. Viral abundance on suspended matter ranges from 105 to 1011 ml-1. The main factors controlling viral abundance are the quality, size and age of aggregates and the exposure time of viruses to aggregates. Other factors such as water residence time likely act indirectly. Overall, aggregates appear to play a role of viral scavengers or reservoirs rather than viral factories. Adsorption of viruses to organic aggregates or inorganic particles can stimulate growth of the free-living prokaryotic community, e.g. by reducing viral lysis. Such mechanisms can affect microbial diversity, food web structure and biogeochemical cycles. Viral lysis of bacterio- and phytoplankton influences the formation and fate of aggregates and can, for example, result in a higher stability of algal flocs. Thus, viruses also influence carbon export; however, it is still not clear whether they short-circuit or prime the biological pump. Throughout this review, emphasis has been placed on defining general problems and knowledge gaps in virus-particle interactions and on providing avenues for further research, particularly those linked to global change.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Exercise tolerance and quality of life in elderly patients with chronic atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common arrhythmia affecting the elderly. Although the risk of cardioembolic stroke is well defined, the effects of chronic atrial fibrillation on exercise tolerance and quality of life have been less well quantified. METHODS: We compared a group of 52 elderly patients with chronic atrial fibrillation to a group of 48 control patients in sinus rhythm. Each patient underwent an interview that incorporated the Short Form-36 Health Survey (SF-36) to quantify individual perceptions on quality of life. In addition each person underwent physiologic testing that included a Modified Bruce Protocol exercise tolerance test, 24-hour ambulatory monitor test, and an echocardiogram. RESULTS: Both groups were elderly, 77 vs 76 years of age (P=0.35). The two groups had similar ejection fractions, 55.4% vs 58.4% (P=0.10). The atrial fibrillation patients demonstrated a higher level of comorbidity based on the Charlson Comorbidity Index, 2.46 vs 1.57 (P=0.03). On formal exercise testing there was no statistical difference in exercise duration between the two groups 9.0 vs 10.1 minutes (P=0.24). Similarly the Physical Summary Score (PCS) and the Mental Summary Score (MCS) of the SF-36 quality of life survey did not demonstrate a statistical difference between the two groups. PCS: 43.0 vs 45.9 (P=0.24); MCS: 52.5 vs 55.7 (P=0.07). CONCLUSIONS: Despite a higher level of comorbidity, elderly, ambulatory patients with chronic atrial fibrillation demonstrate similar exercise tolerance and report similar quality of life to a group of age-matched control patients in sinus rhythm. There is a cohort of patients in chronic atrial fibrillation in whom a strategy of rate control and anticoagulation may be appropriate.

A multicenter two by two factorial trial of cognitive behavioral therapy and aerobic exercise for Gulf War veterans' illnesses: design of a veterans affairs cooperative study (CSP #470).

The Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) Study #470 is a 2 x 2 factorial trial designed to evaluate the hypothesis that both cognitive behavioral therapy (CBT) and aerobic exercise will significantly improve physical function in participants with Gulf War veterans' illnesses (GWVI), and that adding CBT to aerobic exercise will provide further incremental benefit. One thousand three hundred fifty-six veterans will be randomized to one of four treatment arms: CBT plus aerobic exercise plus usual and customary care, aerobic exercise plus usual and customary care, CBT plus usual and customary care, or usual and customary care alone. The study duration is 2.5 years with 1.5 years of intake and 1 year of follow-up. The primary outcome measure is the proportion of veterans improved more than seven units on the physical component summary (PCS) scale of the Short Form Health Survey for Veterans (SF-36V) measured 12 months after randomization. This generic quality-of-life measure was chosen because there is no disease-specific measure for GWVI and the symptoms of GWVI span a wide range of physical manifestations that are related to the domains covered by the PCS scale. Sample size was determined to detect all six pairwise comparisons between the four treatment arms with 90% power and a Bonferroni adjustment for an overall type I error of 0.05 or 0.05/6 = 0.0083. CSP #470 was initiated in May 1999 in 18 VA and two Department of Defense medical centers. To date this represents the largest randomized trial designed to evaluate treatments for individuals with unexplained physical symptoms. This paper will focus on the rationale and unique features of the study design. Control Clin Trials 2001;22:310-332

A nested case-control study of the effectiveness of screening for prostate cancer: research design.

Although prostate-specific antigen (PSA) and digital rectal examination (DRE) are commonly used to screen for prostate cancer, available data do not confirm that either test improves survival. This report describes the methodological aspects of a nested case-control study addressing the question of whether PSA screening, with or without DRE, is effective in increasing survival. Potential sources of bias are discussed, as well as corresponding strategies used to avoid them. Results are expected in the year 2002.

Presenting manifestations, cigarette smoking, and detection bias in age at diagnosis of lung cancer.

PURPOSE: To examine the possible role of detection bias in the association between amount of cigarette smoking and age at diagnosis of lung cancer. The bias can occur because primary lung cancer can often escape detection during life and will be found (if at all) as a "necropsy surprise" unless a diagnostic workup is provoked by such presenting manifestations as hemoptysis and a localized chest lesion. The necropsy surprises will be reduced and the reported rates of pre-mortem incidence will be raised if a cigarette smoking history also acts as a diagnostic incentive. METHODS: This possibility was examined in a case series of 1266 patients whose primary lung cancer had been carefully classified according to diverse features at the time of presentation. For the total case group and for pertinent clinical, anatomic, and demographic subgroups, we then examined the trends for age at diagnosis in relation to amount of cigarette smoking. RESULTS: The overall age at diagnosis (median = 63 years; mean = 61.2) remained essentially similar in five ordinal groups of Tumor, Nodes, Metastases (TNM) and four of five Clinical Severity stages, but had an inverse monotonic gradient in six ordinal groups of customary cigarette smoking [from none to >2 packs per day (ppd)]. Because an earlier age of discovery can be explained by either etiologic or detection-bias roles for heavier smoking, its impact was checked in subgroups with and without diagnostically provocative manifestations. In localized lesions, the smoking-age gradient vanished if suspicious "indicator" symptoms were present, but persisted if they were absent. Regardless of symptoms, the age gradient was strengthened in non-localized cancer lesions where smoking might particularly point to a primary diagnostic source in the lung. CONCLUSIONS: Detection bias may play a distinctive, although often overlooked, role in the work-up decisions that precede and lead to a diagnosis of lung cancer.

Validation of a staging system for evaluating prognosis in prostate cancer.

BACKGROUND: The purposes of our research were to validate a previously published clinical-anatomic staging system for evaluating prognosis in prostate cancer and to explore the predictive ability of additional factors. METHODS: All patients diagnosed with prostate cancer by physicians affiliated with Yale-New Haven Hospital during 1991 were eligible for the study. Patient and tumor characteristics at baseline were extracted from medical records with up to five-year follow-up for mortality. The original system was validated using Cox proportional hazards analysis and conjunctive consolidation. Prostate specific antigen (PSA) and Gleason score were also explored as factors to be included in an updated staging system. RESULTS: Five-year survival was 76% among 121 patients included in the study. The original staging system, when applied to the current cohort, was validated: Five-year survival ranged from 100% (low-risk) to 27% (high-risk). PSA and Gleason score were associated with survival but did not change results substantially in this population. CONCLUSION: By predicting distinct mortality outcomes in men with prostate cancer, prognostic staging systems can be used to help patients and physicians make informed treatment decisions.

Prior healthcare utilization as a predictor of survival for medical intensive care unit patients.

OBJECTIVE: To determine whether measures of inpatient care utilization from the year preceding admission to a medical intensive care unit (MICU) improve physiology-based predictions of hospital and 1-yr survival. DESIGN: Inception cohort study with a validation cohort. SETTING: The MICU in university-affiliated Department of Veterans Affairs Medical Center. PATIENTS: A total of 1,200 consecutive patients admitted to the MICU. MEASUREMENTS AND MAIN RESULTS: Increased use of inpatient health care before MICU admission was associated with increased mortality. However, inpatient utilization data failed to improve physiology-based logistic models for hospital and 1-yr survival (p > .15 for improvement in the area under the receiver operating characteristic curve for both end points in the validation cohort), whereas physiologic data improved models derived from measures of inpatient care (p < .001 for both end points). Empirically derived inpatient care models used only information from the few days preceding MICU admission, despite the availability of a full year of data. CONCLUSIONS: Chronic illness, as gauged by a need for frequent inpatient care in the year before MICU admission, is not independently predictive of poor short- or long-term survival. Clinicians should not attempt to predict survival of prospective MICU patients by the extent of previous inpatient care.

Alcohol exposure and health services utilization in older veterans.

The objective of this study was to determine if increased alcohol exposure is associated with greater use of health services among older veterans. A total of 129 older veterans (> or =65 years old), receiving longitudinal care in a Veterans' Administration primary care clinic, were followed retrospectively for up to 42 months. Subjects were screened at baseline for problem drinking with the CAGE or the quantity-frequency questions from the Alcohol Use Disorders Identification Test (QF-AUDIT), and stratified by exposure into three categories: abstainers, social drinkers, and problem drinkers. Outcomes included total outpatient clinic visits, laboratory tests, radiologic and other technologic procedures, as well as acute care hospitalizations. For all subjects (N = 129), no association was found between alcohol exposure and use of any outpatient services. Among CAGE-screened (n = 62) abstainers, social drinkers, and problem drinkers, significant differences were found in the median number of laboratory tests (7.3 vs. 3.4 vs. 7.1, P = 0.004) and hospitalizations (0.3 vs. 0.0 vs. 0.3, P = 0.001) per patient year of follow-up. No exposure-outcome associations were present, however, among QF-AUDIT-screened subjects (n = 67). We were unable to demonstrate a consistent relationship between alcohol exposure and health services utilization. The effects of alcohol on older veterans' use of health services varied with the method used to measure alcohol exposure. Additional studies are needed to determine whether multiple, or possibly new, measures can more precisely define the health effects of alcohol in older populations.

Immunotherapy of sepsis: flawed concept or faulty implementation?

Gram-negative bacillary sepsis is a leading cause of death among patients hospitalized in intensive care units. While initial clinical studies with the passive administration of anti-endotoxin core-glycolipid (CGL) antibodies for the treatment and prophylaxis of sepsis showed promising results, subsequent studies failed to show a consistent benefit. There appears to be a good correlation between anti-CGL antibody levels at the onset of sepsis and maintenance of antibody levels during sepsis with outcome. Previous clinical studies may have failed because insufficient amounts of antibody were administered early in the course of sepsis. Unlike the case with anti-CGL antibodies, polyvalent, hyperimmune type-specific antibody preparations may prevent the development of infections; however, these antibodies also must be provided in adequate amounts and in close proximity to infection in order to provide a beneficial effect. These pharmacokinetic requirements may limit the utility of passive immunotherapy for the prophylaxis of sepsis. Active immunization of acutely traumatized patients or of rats subsequently rendered neutropenic with cyclophosphamide induced high antibody levels for extended periods of time. Since trauma and other conditions are associated with a Th(2) response, these conditions may favor antibody formation following active immunization. Active immunization with both anti-CGL and/or polyvalent-specific vaccines for the prophylaxis of sepsis with passive supplementation at the onset of sepsis is an approach that merits further investigation.

Informed consent for PSA screening: does it happen?

CONTEXT: Screening for prostate cancer with serum prostate-specific antigen (PSA) is controversial. Ideally, patients should be aware of the potential benefits and risks related to testing. PURPOSE: To assess whether patients remembered having PSA screening and to determine whether they recalled having a discussion with their primary care provider about the pros and cons of such testing. METHODS: A questionnaire was sent to patients who had PSA screening ordered by a primary care practitioner during a 2-month period at a university-affiliated Veterans Affairs medical center. Approximately 3 months after the PSA test was done, patients were asked about their baseline health as well as their knowledge of and attitudes toward screening with PSA and treatment for prostate cancer. RESULTS: The overall response rate was 197 out of 421 (46%) patients. Among 173 eligible respondents without prostate cancer, 53 (31%) were unaware that their physician had ordered a PSA test. Among the 120 patients who were aware of receiving the test, only 56 (47%) recalled having a discussion with their primary care provider about the risks and benefits of screening. Support for the test was more common among patients who recalled having PSA screening than those who did not recall having the test (91% vs. 70%, respectively; P = 0.003). CONCLUSIONS: Patients who have PSA screening often are unable to recall relevant facts about the test and may have no knowledge of its associated risks and benefits. The role and effectiveness of obtaining verbal informed consent for PSA screening should be re-evaluated.

Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing.

BACKGROUND: Community-acquired bacterial meningitis causes substantial morbidity and mortality in adults. OBJECTIVE: To create and test a prognostic model for persons with community-acquired bacterial meningitis and to determine whether antibiotic timing influences clinical outcome. DESIGN: Retrospective cohort study; patients were divided into derivation and validation samples. SETTING: Four hospitals in Connecticut. PATIENTS: 269 persons who, between 1970 and 1995, had community-acquired bacterial meningitis microbiologically proven by a lumbar puncture done within 24 hours of presentation in the emergency department. MEASUREMENTS: Baseline clinical and laboratory features and times of arrival in the emergency department, performance of lumbar puncture, and administration of antibiotics. The target end point was the development of an adverse clinical outcome (death or neurologic deficit at discharge). RESULTS: For the total group, the hospital mortality rate was 27%. Fifty-six of 269 patients (21 %) developed a neurologic deficit, and in 9% the neurologic deficit persisted at discharge. Three baseline clinical features (hypotension, altered mental status, and seizures) were independently associated with adverse clinical outcome and were used to create a prognostic model from the derivation sample. The prediction accuracy of the model was determined by using the concordance index (c-index). For both the derivation sample (c-index, 0.73 [95% CI, 0.65 to 0.81]) and the validation sample (c-index, 0.81 [CI, 0.71 to 0.92]), the model predicted adverse clinical outcome significantly better than chance. For the total group, the model stratified patients into three prognostic stages: low risk for adverse clinical outcome (9%; stage I), intermediate risk (33%; stage II), and high risk (56%; stage III) (P=0.001). Adverse clinical outcome was more common for patients in whom the prognostic stage advanced from low risk (P=0.008) or intermediate risk (P=0.003) at arrival in the emergency department to high risk before administration of antibiotics. CONCLUSIONS: In persons with community-acquired bacterial meningitis, three baseline clinical features of disease severity predicted adverse clinical outcome and stratified patients into three stages of prognostic severity. Delay in therapy after arrival in the emergency department was associated with adverse clinical outcome when the patient's condition advanced to the highest stage of prognostic severity before the initial antibiotic dose was given.

Twenty-two-year follow-up in the VA Cooperative Study of Coronary Artery Bypass Surgery for Stable Angina.

We evaluated the 22-year results of initial coronary artery bypass surgery with saphenous vein grafts compared with initial medical therapy on survival, incidence of myocardial infarction, reoperation, and symptomatic status in 686 patients (average age 51) with stable angina in the Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery. Between 1972 and 1974, 354 patients were assigned to medical treatment and 332 to surgical revascularization. In the surgical cohort, 312 patients underwent operation (operative mortality 5.8%) and 25% subsequently underwent repeat operation (operative mortality 10.3%). In the medical cohort, 160 patients crossed over to surgery (operative mortality 4.4%) and 21% of these patients had reoperation (operative mortality 9.1%). Neither crossover nor reoperation was predictable by angiographic or clinical risk factors measured at baseline. The overall 22-year cumulative survival rates were 25% and 20% in the medical and surgical cohorts (p = 0.24). Corresponding rates in low-risk patients who had 1 or 2 vessels diseased, or 3 vessels diseased with normal left ventricular function were 31% and 24% (p = 0.024). Although significant at 10 years, there was also no long-term survival benefit for high-risk patients assigned to bypass surgery. The probabilities of remaining free of myocardial infarction and of being alive without infarction were significantly higher with initial medical therapy, 57% versus 41% (p = 0.02) and 18% versus 11% (p = 0.0031), respectively. This trial provides strong evidence that initial bypass surgery did not improve survival for low-risk patients, and that it did not reduce the overall risk of myocardial infarction. Although there was an early survival benefit with surgery in high-risk patients (up to a decade), long-term survival rates became comparable in both treatment groups. In total, there were twice as many bypass procedures performed in the group assigned to surgery without any long-term survival or symptomatic benefit.

Importance of functional measures in predicting mortality among older hospitalized patients.

CONTEXT: Measures of physical and cognitive function are strong prognostic predictors of hospital outcomes for older persons, but current risk adjustment and burden of illness assessment indices do not include these measures. OBJECTIVE: To evaluate and validate the contribution of functional measures to the ability of 5 standard burden of illness indices (Charlson, Acute Physiology and Chronic Health Evaluation [APACHE] II, Disease Staging, All Patient Refined Diagnosis Related Groups, and a clinician's subjective rating) in predicting 90-day and 2-year mortality among older hospitalized patients. DESIGN: Two prospective cohort studies. SETTING: General medicine service, university teaching hospital. PATIENTS: For the development cohort, 207 consecutive patients aged 70 years or older, and for the validation cohort, 318 comparable patients. MAIN OUTCOME MEASURE: Death within 90 days and 2 years from the index admission. RESULTS: In the development cohort, 29 patients (14%) and 81 patients (39%) died within 90 days and 2 years, respectively. A functional axis was developed using 3 independent risk factors: impairment in instrumental activities of daily living, Mini-Mental State Examination score of less than 20, and shortened Geriatric Depression Scale score of 7 or higher, creating low-, intermediate-, and high-risk groups with associated mortality rates of 20%, 32%, and 60%, respectively (P<.001); the C statistic for the final model was 0.69. The corresponding mortality rates in the validation cohort, in which 59 (19%) and 138 (43%) died within 90 days and 2 years, respectively, were 24%, 45%, and 60% (P<.001); the C statistic for the final model was 0.66. For each burden of illness index, the functional axis contributed significantly to the predictive ability of the model for both 90 days and 2 years. When the functional axis and each burden of illness measure were analyzed in cross-stratified format, mortality rates increased progressively from low-risk to high-risk functional groups within strata of burden of illness indices (double-gradient phenomenon). The contributions of functional and burden of illness measures were substantive and interrelated. CONCLUSIONS: Functional measures are strong predictors of 90-day and 2-year mortality after hospitalization. Furthermore, these measures contribute substantially to the prognostic ability of 5 burden of illness indices. Optimal risk adjustment for older hospitalized patients should incorporate functional status variables.

Combination Hemotherapy and Mortality Prevention (CHAMP) Study Rationale and Design.

It is now agreed that the majority of acute myocardial infarctions result from intracoronary thrombosis at sites of atherosclerotic plaque that have been disrupted. In 1947 Nicol and Fassett published the first clinical paper suggesting that agents interfering with blood coagulation could prevent myocardial infarction in patients at risk. Scores of subsequent clinical trials were performed to assess the efficacy of anticoagulants and antiplatelet agents in preventing death and reinfarction in survivors of acute myocardial infarction. Despite these efforts no agreement exists on whether these strategies are beneficial and, if so, which is superior. The primary obstacle to progress in this field has been the failure of nearly all trials to enroll the large numbers of subjects required to demonstrate a survival benefit. The large sample size requirement derives from two inescapable facts: mortality rates following acute infarction, though variable, are generally low and the potential benefit of these agents in preventing mortality is small. Combining oral anticoagulants with antiplatelet agents (combination hemotherapy) may significantly enhance their antithrombotic effect. Clinical trials of combination hemotherapy have demonstrated superiority over anticoagulant monotherapy in the setting of stroke prevention in patients with prosthetic heart valves. Similar benefit was not observed in trials studying stroke prevention in nonvalvular atrial fibrillation and vascular morbidity in patients surviving an acute myocardial infarction. The failure of these latter studies may relate to the particularly low intensity of warfarin administered in combination with aspirin. This trial proposes to demonstrate that the combination of oral anticoagulation, administered in a moderate dose intensity, and antiplatelet therapy is superior to aspirin monotherapy in reducing overall mortality following acute myocardial infarction.

Statistical evaluation of the role of Helicobacter pylori in stress gastritis: applications of splines and bootstrapping to the logistic model.

Stress gastritis is a serious problem in the intensive care unit population. The recent discovery of the causal nature of Helicobacter pylori (H. pylori) in the development of gastric ulcers led us to examine its relationship with stress gastritis. We investigated this relationship in 874 veterans admitted to intensive care units who were tested for the presence of H. pylori and followed for 6 weeks for the development of stress gastritis. We fit spline models to assess functional relationships and used the logistic model to determine the association between H. pylori and stress gastritis. The predictive ability of the model was assessed with receiver operating characteristic (ROC) curve analysis and validated with the bootstrapping technique. Increased anti-H. pylori immunoglobulin A concentrations were found to be an important predictor of stress gastritis independent of other known risk factors.

A review of the design of vaccine efficacy trials and a proposal for the design of the VA Cooperative Study of Active Immunotherapy of HIV Infection.

We review the design of vaccine trials based on a search of the medical literature over the past four years, and present the proposed design of a therapeutic HIV vaccine efficacy study by the Department of Veterans Affairs Cooperative Studies Program. We explore the reasons for the atypical design of many vaccine trials, particularly the analysis of efficacy and how it differs from the more usual intent-to-treat analysis used in nonvaccine trials.

Magnitude and duration of the effect of sepsis on survival. Department of Veterans Affairs Systemic Sepsis Cooperative Studies Group.

OBJECTIVE: To determine the magnitude and duration of the effects of sepsis on survival. DESIGN: Cohort study. SETTING: The 10 Department of Veterans Affairs Medical Centers of the Systemic Sepsis Cooperative Studies Group, which from 1983 to 1986 conducted the Department of Veterans Affairs Cooperative Study of Corticosteroids in Systemic Sepsis. PATIENTS: The septic population consisted of 1505 patients with evaluable data from the screening log of the Cooperative Study of Corticosteroids in Systemic Sepsis. All 91830 nonpsychiatric, noninfected patients discharged from the participating medical centers between October 1, 1984, and September 30, 1985, were included in the control population. MAIN OUTCOME MEASURE: Death through 8 years after the index hospitalization. RESULTS: On the basis of a proportional hazards model constructed from the demographic and illness characteristics of the control population, the septic population was at significant risk of dying of nonseptic causes (26% predicted 1-year mortality). In the septic population, the daily risk of dying exceeded predictions from this model for 5 years, and the hazard rate rose with increasing severity of the septic episode throughout the first year (P<.05). Among 30-day survivors, sepsis reduced the remaining mean life span from a predicted 8.03 years to 4.08 years. CONCLUSIONS: Sepsis not only causes deaths acutely, but also increases the risk of death for up to 5 years after the septic episode even after comorbidities are accounted for. The risk of late death during the first year is associated with the severity of the septic episode.