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Natural history of viral markers in children infected with human T lymphotropic virus type I in Jamaica.

PURPOSE: We conducted a longitudinal analysis of human T lymphotropic virus type I (HTLV-I) viral markers in 28 Jamaican mothers and their children, who were monitored for a median of 6.2 years after the birth of the children. METHODS: The HTLV-I provirus DNA load was measured using the Taqman system (PE Applied Biosystems). The HTLV-I antibody titer was determined using the Vironstika HTLV-I/II Microelisa System (Organon Teknika). The HTLV-I Tax-specific antibody titers were measured using an enzyme-linked immunosorbent assay. Generalized estimating equations were used to describe the associations of exposure variables with sequentially measured levels of HTLV-I viral markers in children. RESULTS: The HTLV-I antibody titer increased significantly up to 1 year after infection, reaching equilibrium at a median titer of 1 : 7,786. The prevalence of Tax-specific antibody reached 80% at 2 years after infection. The provirus load increased up to 2 years after infection, reaching equilibrium at a median of 6,695 copies/100,000 peripheral blood mononuclear cells. The increase in the provirus load was significant only among children with eczema, but not among children without eczema. CONCLUSIONS: The provirus loads in children increased for an additional year after their antibody titers had stabilized, possibly as a result of the expansion of HTLV-I-infected clones. This effect was significant only for children with eczema. Among HTLV-I-infected children, eczema may be a cutaneous marker of the risk of HTLV-I-associated diseases developing in adulthood.

Breast Feeding↗

Novel deletion of HIV type 1 reverse transcriptase residue 69 conferring selective high-level resistance to nevirapine.

A novel deletion of residue 69 of the HIV-1 reverse transcriptase (RT) gene was detected in combination with mutations V75I/V and F77L/F in a patient with partial virological response to several antiretroviral drug regimens, including stavudine (D4T), didanosine (DDI), lamivudine (3TC), saquinavir (SQV), and nevirapine (NVP). Longitudinal analysis of samples revealed that this deletion emerged upon reinitiation DDI/D4T therapy following a toxicity-induced short discontinuation of all antiretrovirals. Analysis of the resistance phenotype showed a greater than 62-fold increase of the IC50 of NVP, but no significant change in sensitivity to other single nonnucleoside reverse transcriptase inhibitors (NNRTIs). The mutated virus showed only a moderately reduced sensitivity to DDI (6.7-fold) and D4T (4.8 fold). In a subsequent sample 3 months later additional RT mutations were found, including A62V, Y188L, and Q151M, conferring high-level cross-resistance to multiple nucleoside analogs. Our findings provide evidence that the deletion of RT residue 69 selectively confers high-level NVP resistance.

Adult↗

Challenges in improving fitness: results of a community-based, randomized, controlled lifestyle change intervention.

OBJECTIVE: This study tested the efficacy of an 8-week culturally targeted nutrition and physical activity intervention on body composition. METHODS: A randomized, attention-controlled, two-group trial was conducted in a blackowned commercial gym with a sample of 366 predominantly healthy, obese African American women. A free 1-year membership to the study site gym was provided to participants in both groups. Data were collected at baseline, 2, 6, and 12 months. RESULTS: Sample retention at 1 year was 71%. Between-group longitudinal analysis including only participants with complete data revealed a trend toward weight stability in the intervention group at 2 months compared with controls (+0.05 kg/m(2), p = 0.75; +0.32 kg/m(2), p = 0.08, respectively), disappearing at 12 months (+1.37 kg/m(2), p = 0.0001; +1.02 kg/m(2), p = 0.001, respectively). Within-group analysis demonstrated that intervention and control participants' fitness (1-mile run-walk) improved by 1.9 minutes (p = 0.0001) and 2.3 minutes (p = 0.0001), respectively, at 12 months. Mixed model regression analyses demonstrated a significant main effect of the intervention on fitness (p = 0.0185) and a marginally significant effect on body mass index (BMI) (p = 0.057), at 2 months, disappearing by 6 months. By 12 months, however, the controls exhibited a significant advantage in waist circumference stability compared with intervention participants (+1.1 cm, p = 0.2763; +2.1 cm, p = 0.0002, respectively). CONCLUSIONS: The intervention produced modest short-term improvements in body composition, but the economic incentive of a free 1-year gym membership provided to all participants was a more potent intervention than the education and social support intervention tested. However, longer-term fitness enhancement remains elusive and demands research and policy attention. These findings have policy implications in that employer-/insurer-subsidized gym memberships may require interventions targeting other levels of change (e.g., physical or social/environmental) to foster sustainable fitness improvements.

Adult↗

Neuroprotective effects of basic fibroblast growth factor following spinal cord contusion injury in the rat.

Cytokines and neurotrophic factors have been implicated in the pathophysiology of injury to the central nervous system. While some cytokines are considered pro-inflammatory, other factors promote neuronal growth and survival. The present study investigated the neuroprotective effects of interleukins 1 (IL-1), 4 (IL-4), and 6 (IL-6), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and basic fibroblast growth factor (bFGF) in a contusion model of spinal cord injury. Female Sprague-Dawley rats (n = 55) sustained a 10-g weight-drop injury to the lower thoracic spinal cord (T10) from a height of 12.5 mm using the NYU impactor. A micro-infusion system (Alzet minipump) was used to continuously deliver drugs or vehicle directly into the epicenter of the contused spinal cord starting 1 or three h postinjury. At the end of 7 days, animals were perfused and the cords removed for histopathological analysis. Longitudinal serial sections were cut on a freezing microtome and stained with cresyl violet. Areas of central necrosis, partial preservation, and total zone of tissue injury were identified and traced by an independent reviewer using a computer based imaging system. The mean total zone of injury in five animals receiving vehicle infusion was 18.04+/-4.20 mm3. The mean zone of partial preservation in these animals was 16.46+/-3.32 mm. Basic fibroblast growth factor reduced the total zone of injury by 33% [p<0.01, least significant difference (LSD) of Fisher] in five animals and the zone of partial preservation by 32% (p<0.01, LSD of Fisher) when compared to controls. There were trends toward reduction in total zone of injury and zone of partial preservation in rats treated with IL-4, CNTF, and NGF versus vehicle; however, none of these reached statistical significance. No significant differences were observed between animals receiving vehicle versus bFGF treatment commencing 3 h after injury. These data demonstrate that the continuous intramedullary infusion of bFGF initiated one hour after moderate contusion injury of the spinal cord significantly reduces the total zone of injury and the zone of partial preservation. These results support the further investigation and possible future clinical application of bFGF in the treatment of acute spinal cord contusion injury.

Animals↗

Targeting recovery: priorities of the spinal cord-injured population.

In the United States alone, there are more than 200,000 individuals living with a chronic spinal cord injury (SCI). Healthcare for these individuals creates a significant economic burden for the country, not to mention the physiological, psychological, and social suffering these people endure everyday. Regaining partial function can lead to greater independence, thereby improving quality of life. To ascertain what functions are most important to the SCI population, in regard to enhancing quality of life, a novel survey was performed in which subjects were asked to rank seven functions in order of importance to their quality of life. The survey was distributed via email, postal mail, the internet, interview, and word of mouth to the SCI community at large. A total of 681 responses were completed. Regaining arm and hand function was most important to quadriplegics, while regaining sexual function was the highest priority for paraplegics. Improving bladder and bowel function was of shared importance to both injury groups. A longitudinal analysis revealed only slight differences between individuals injured <3 years compared to those injured >3 years. The majority of participants indicated that exercise was important to functional recovery, yet more than half either did not have access to exercise or did not have access to a trained therapist to oversee that exercise. In order to improve the relevance of research in this area, the concerns of the SCI population must be better known and taken into account. This approach is consistent with and emphasized by the new NIH roadmap to discovery.

Activities of Daily Living↗

Genotype-structure-phenotype correlations define divergent natural history in early-onset spastic paraplegia type 4.

Hereditary spastic paraplegia type 4 (SPG4), caused by variants in SPAST, is the most common form of HSP and exhibits a remarkable phenotypic heterogeneity ranging from late-onset pure presentations to severe, early-onset complex disease. Robust genotype-phenotype correlations and detailed natural history data are lacking, limiting clinical trial readiness. We analyzed 206 patients with genetically confirmed SPG4 enrolled across seven international centers, complemented by high-quality literature-derived cases. Deep phenotyping included standardized motor scales, spasticity ratings, developmental milestones, and patient-reported outcomes. We developed an extended essentiality-mapping framework to classify SPAST missense variants by integrating in silico pathogenicity predictions, evolutionary constraint, physicochemical residue connectivity, and variant enrichment within the human spastin hexamer structure. Plasma neurofilament light chain (pNfL) using was quantified using Simoa in 26 patients and 101 controls. We identified 136 distinct SPAST variants, including 10 novel variants. Variant class segregated strongly by inheritance, with de novo cases enriched for missense variants and inherited cases showing a variety of variant classes with enrichment for truncating variants. Longitudinal analysis revealed two latent trajectories: a rapidly progressive severe subgroup enriched for de novo missense variants, and a biphasic moderate subgroup enriched for inherited truncating variants. Patient stratification integrating spastin essentiality mapping (missense variants affecting essential, neutral, or context-dependent residues) with established genetic modifiers (biallelic pathogenic variants or modifier variants in trans) classified patients into predicted severe and moderate subgroups with divergent age at onset and clinical disease progression. The severe subgroup showed early developmental delays, rapid loss of ambulation, and declining quality of life, while the moderate subgroup displayed delayed but accelerating disease progression. pNfL levels were elevated in both subgroups, most pronounced in severe early disease. This study provides the most detailed natural history of SPG4 to date and introduces a biologically informed stratification framework that links variant class and location to divergent clinical trajectories. These data establish clinically meaningful benchmarks and offer a genotype-based framework to improve anticipatory care and optimize trial design for SPG4.

SPAST↗

Driving cessation and increased depressive symptoms.

BACKGROUND: To understand the consequences of driving cessation in older adults, the authors evaluated depression in former drivers compared with active drivers. METHODS: Depression (as assessed using the Center for Epidemiological Studies Depression Scale), driving status, sociodemographic factors, health status, and cognitive function were evaluated for a cohort of 1953 residents of Sonoma County, California, aged 55 years and older, as part of a community-based study of aging and physical performance. The authors re-interviewed 1772 participants who were active drivers at baseline 3 years later. RESULTS: At baseline, former drivers reported higher levels of depression than did active drivers even after the authors controlled for age, sex, education, health, and marital status. In a longitudinal analysis, drivers who stopped driving during the 3-year interval (i.e., former drivers) reported higher levels of depressive symptoms than did those who remained active drivers, after the authors controlled for changes in health status and cognitive function. Increased depression for former drivers was substantially higher in men than in women. CONCLUSIONS: With increasing age, many older adults reduce and then stop driving. Increased depression may be among the consequences associated with driving reduction or cessation.

Accidents, Traffic↗

Aging and voluntary association participation.

This longitudinal analysis examines changes in voluntary association participation levels over a 4-year period using data from the middle age of the Duke Adaptation Study (N=374) and over a 2 1/2-year period using data from a study of older persons in Oberlin, Ohio (N=104). The findings showed; the extent of participation was high in both samples; mean levels of participation remained essentially unchanged; persons with stable or increasing participation levels outnumbered those with declining levels; and persons not participating at the time of the initial interview were unlikely to be participating later, while those who were participating initially were likely to have continued their participation. Contrary to predictions of declining activity based on disengagement theory, aging appears to be accompanied by stability and continuity in levels of voluntary association participation.

Adult↗

Age differences in self-assessments of health: age changes, cohort differences, or survivorship?

Do older people tend to exaggerate their health problems? Or do they downplay them? Do such tendencies change as people age? Are they a function of cohort membership? Or are differences in health perceptions among elderly people due to differences in survivorship within the elderly cohorts? These questions are examined with longitudinal data from the Yale Health and Aging Project, a stratified probability sample of elderly persons in New Haven, Connecticut. Complete health assessments are available for 2,583 community residents 65 and older in 1982, and complete follow-up date are available for 1,319 respondents in 1988. Multivariate regressions of self-assessed health on concurrent 1982 and 1988 objective health status and longitudinal analysis of residual values from these equations show that: (a) older survey respondents gave disproportionately positive health assessments, and (b) processes of aging, selective survivorship, and cohort differences all appear to play a role in creating this pattern.

Aged↗

Evaluating the effectiveness of health promotion policy: changes in the law on drinking and driving in California.

The purpose of the study was to determine the utility of general population health surveillance data for evaluating broad policy changes that relate to health promotion. Data were drawn from the United States (US) Behavioral Risk Factor Surveillance System (BRFSS) for one US state, California. Because these data are collected frequently and continually, a quasi-experimental approach to the evaluation was possible using a type of interrupted time series analysis or longitudinal impact analysis. A statistically significant decrease in the number of declared episodes of drinking and driving was found after enactment of new state policy. These findings were compared and found consistent with another study in California that examined the effect of changes in the law on alcohol-related traffic accidents. Our findings suggest that data from a behavioral surveillance system, in this case the BRFSS, are useful to evaluate the effect of a health promotion intervention. Further, the study demonstrates the utility of comparing different data sources when assessing a population-wide change in health promotion policy.

Alcohol Drinking↗

Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 microg ethinyl estradiol and 3 mg drospirenone.

BACKGROUND: The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone. METHODS: A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles. RESULTS: Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences. CONCLUSION: NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweight.

Administration, Oral↗

Measurement of human herpesvirus 7 load in peripheral blood and saliva of healthy subjects by quantitative polymerase chain reaction.

Qualitative and competitive-quantitative nested polymerase chain reaction (PCR) assays were developed for human herpesvirus 7 (HHV-7). These assays amplify a DNA sequence encoding part of the HHV-7 homologue of the human herpesvirus 6 (HHV-6) U42 gene. The PCR assays were used to analyze peripheral blood DNA (pbDNA) and saliva from 24 healthy volunteers. The prevalence of HHV-7 in saliva was 96%, with a median virus load of 1.1 x 10(6) copies/mL. Longitudinal analysis revealed sustained virus load, suggesting continued active viral replication. Analysis of 1 microgram of pbDNA showed the prevalence of HHV-7 to be 83%, with a median virus load of 40 copies (267 copies/10(6) cells). Analysis of sequential pbDNA samples showed individuals to have stable levels of HHV-7 virus load. These data demonstrate persistence of HHV-7 at two distinct sites and provide baseline data allowing comparisons with HHV-7 load in immunocompromised patients.

Base Sequence↗

Dynamics of the nutrition transition toward the animal foods sector in China and its implications: a worried perspective.

Many changes in diet and in physical activity are occurring simultaneously in the developing world. These diet shifts include large increases in energy density, in the proportion of the population consuming a high fat diet and in animal product intake. Animal source foods (ASF) play a major role in these diet shifts. This article documents the large shifts in the composition of diets and obesity across the developing world and notes that these changes are accelerating. Using China as a case study, evidence of the speeding up of this process is presented in descriptive and more rigorous dynamic longitudinal analysis. The implications of these changes for dietary and obesity patterns and cardiovascular disease are great. Indeed, developing countries are at a point where the prevalence of obesity is greater than that of undernutrition and concerns related to intake of saturated fat and energy imbalance must be considered more seriously by the agriculture sector. Current agriculture development policy in many developing countries focuses on livestock promotion and does not consider the potential adverse health consequences of this strategy. Although linkages between ASF intake and obesity cannot be established as clearly as they are for high ASF intakes, heart disease and cancer, the potential adverse health effects linked with an increased ASF intake should no longer be ignored.

Adult↗

Who's number one? The impact of variability on rankings based on public health indicators.

OBJECTIVE: Researchers, government, and the press often rank jurisdictions according to public health indicators; however, measures of uncertainty rarely accompany these comparisons. To demonstrate the variability associated with rankings that use public health measures, the authors examined the uncertainty associated with ranks based on three common methods used to derive public health indicators: age-adjustment, calculations based on census estimates, and calculations based on survey data. METHODS: The authors observed the effect of changing the standard population from the 1970 population to the 1997 population on rank-order lists of jurisdictions according to age-adjusted 1998 mortality rates. They used a Monte Carlo method to calculate confidence intervals (CIs) around ranks based on census estimates of 1998 infant mortality rates and based on 1999 Behavioral Risk Factor Surveillance System (BRFSS) survey data on the prevalence of hypertension. RESULTS: Changing the standard year from 1970 to 1997 resulted in a shift of at least three rank-order positions for seven states. Two states shifted five positions. CIs associated with ranking by infant mortality rates were broad, with a mean of 16 ranks. CIs around ranks for the prevalence of hypertension were also wide, with a mean of 18 ranks. CONCLUSION: While ranking based on public health indicators is an attractive and popular way of presenting public health data, caution and close examination of the underlying data are needed for proper interpretation. Alternative methods, such as longitudinal analysis or comparisons with standards, may prove more useful.

Age Factors↗

Decline in sexually transmitted disease prevalence in female Bolivian sex workers: impact of an HIV prevention project.

OBJECTIVE: To implement an HIV prevention intervention among female commercial sex workers (CSW), and to monitor key outcomes using routinely collected clinical and laboratory data. DESIGN: Cross-sectional and longitudinal analysis of data from an open-enrollment cohort. SETTING: One public sexually transmitted disease (STD) clinic and about 25 brothels in La Paz, Bolivia. PARTICIPANTS: A total of 508 female CSW who work at brothels and attend a public STD clinic. INTERVENTION: Improved STD clinical care, supported by periodic laboratory testing, and behavioral interventions performed by a local non-governmental organization. MAIN OUTCOME MEASURES: Prevalence of gonorrhea, syphilis (reactive plasma reagin titer > or = 1 : 16), genital ulcer disease, chlamydial infection, and trichomoniasis; self-reported condom use in the previous month; and HIV seroprevalence. RESULTS: From 1992 through 1995, prevalence of gonorrhea among CSW declined from 25.8 to 9.9% (P < 0.001), syphilis from 14.9 to 8.7% (P = 0.02), and genital ulcer disease from 5.7 to 1.3% (P = 0.006); trends in prevalence of chlamydial infection and trichomoniasis were not significant. Self-reported condom use during vaginal sex in the past month increased from 36.3 to 72.5% (P < 0.001). In a multivariate analysis, condom use was inversely associated with gonorrhea [odds ratio (OR), 0.63; 95% confidence interval (Cl), 0.41-0.97], syphilis (OR, 0.39; 95% Cl, 0.23-0.64), and trichomoniasis (OR, 0.44; 95% Cl, 0.32-0.71). In 1995, HIV seroprevalence among CSW was 0.1%. CONCLUSION: Effective prevention interventions for female CSW can be implemented through public services and non-governmental organizations while HIV rates are still low, and key outcomes can be monitored using data obtained from periodic screening examinations.

Adult↗

Correlates of enrollment in methadone maintenance treatment programs differ by HIV-serostatus.

OBJECTIVES: To identify correlates of enrollment in methadone maintenance treatment programs (MMTP) among a prospective cohort of injection drug users (IDUs) in Baltimore, Maryland. METHODS: A total of 1480 IDUs undergoing semi-annual HIV tests and interviews were studied between 1994 and 1998, during which time a needle exchange program was introduced. Longitudinal analysis using generalized estimating equations was used to identify correlates of MMTP participation over time. RESULTS: Although similar proportions of HIV-seropositive and -seronegative IDUs enrolled in MMTP during follow-up (26 versus 22%, respectively), correlates of enrollment differed by HIV-serostatus. Among HIV-seropositive participants, older age [adjusted odds ratio (AOR, 1.37)] was associated with enrollment in MMTP. Among HIV-seronegative IDUs, factors associated with not enrolling in MMTP were being African American (AOR, 0.22) and having been recently incarcerated (AOR, 0.62) or homeless (AOR, 0.72). In both groups, females were twice as likely to be enrolled in MMTP, and those with Medicaid were 1.5 times more likely to be enrolled. When behavioral factors were lagged one visit, needle exchange program attendance was positively associated with MMTP enrollment among HIV-negative IDUs (AOR, 2.10); however, this association diminished significantly over time as dedicated treatment slots for needle exchange program participants became saturated. CONCLUSIONS: These findings underscore the need to improve access to MMTP, especially to certain subgroups such as African-Americans, the homeless, incarcerated and uninsured. Our data suggest that health care providers and needle exchange programs can facilitate enrollment into MMTP provided that adequate treatment slots are consistently available to this particularly vulnerable population.

Adult↗

Assessment of longitudinal changes in HIV-specific effector activity in subjects undergoing untreated primary HIV infection.

BACKGROUND: Despite the failure of HIV-specific cell-mediated immune responses to clear the virus, these cells play a critical role in the control of viral replication throughout HIV infection. OBJECTIVE: To characterize the natural evolution of the HIV-specific immune response in HIV primary infection (PI). METHODS: Untreated individuals, recruited in HIV PI, were monitored for the evolution of HIV-specific immune responses starting in early HIV disease. Longitudinal analysis of changes in the magnitude and breadth of HIV-specific responses to a panel of MHC class I-restricted peptides was performed using the quantitative interferon-gamma ELISPOT assay. RESULTS: Although immune responses were detected in all individuals at all times tested, the pattern of the immune responses differed significantly from that seen in subjects treated in PI. Untreated PI subjects exhibited dramatic changes with time in the frequency of individual HIV peptide-specific T-cell responses. In contrast HIV-specific immunity was stable in subjects treated in early PI or decreased in intensity and breadth in individuals treated later in PI. In untreated subjects the overall magnitude of HIV-specific reactivity persisted over at least 12 months whereas the number of peptides recognized declined. CONCLUSION: Given that a significant relationship existed between the magnitude of the HIV-specific response and viral load, it is likely that these effector cell expansions and contractions are driven by changes in antigen load.

Adolescent↗

Time course and prognostic significance of hemostatic changes in sepsis: relation to tumor necrosis factor-alpha.

OBJECTIVES: To describe the time course and prognostic significance of tumor necrosis factor-alpha (TNF-alpha) levels and hemostatic abnormalities in clinical sepsis. DESIGN: Prospective, observational study with sequential measurements in an inception cohort. SETTING: An emergency department in a university teaching hospital. Patients were followed up until they either left the hospital or died. PATIENTS: During a 1-yr period, 43 adult patients were selected from all emergency department patients who met the established criteria for sepsis. Excluded were patients with either organ dysfunction or septic shock at the time of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected serially (day of admission and on days 3, 5, and 7) to determine TNF-alpha, platelet count, fibrinogen, factor VII, antithrombin III, tissue-type plasminogen activator activity, plasminogen activator inhibitor activity, plasminogen, and alpha2-antiplasmin. Fibrinopeptide A was measured only on the day of admission. Data were analyzed to determine whether admission values or serially obtained values within 7 days were useful in predicting outcome. Thirteen patients died and 30 survived. On admission, assay values indicated that platelet count and antithrombin III were significantly lower than normal (as observed in 50 healthy adults). Fibrinogen, plasminogen activator inhibitor type 1, tissue-type plasminogen activator, fibrinopeptide A, and TNF-alpha were higher than normal, whereas concentrations of factor VII, plasminogen, and alpha2-antiplasmin were in the normal range. No differences were detected in the admission values between survivors and nonsurvivors, except for antithrombin III. However, subsequent values of some variables demonstrated a difference between survivors and nonsurvivors. Survivors showed increasing platelet count and antithrombin III values compared with nonsurvivors, in whom the values remained low, with no significant changes during the study period. High TNF-alpha levels were found in both groups, but only survivors experienced progressive decrease during the observation period. CONCLUSIONS: Early clinical sepsis is characterized by high plasma levels of TNF-alpha and by activation of the coagulation and fibrinolysis systems. Longitudinal analysis of some variables (antithrombin III, platelet count, and TNF-ea) showed some differences with time between the survivor and nonsurvivor groups, but we feel that such differences were not large enough to be predictive in individual patients.

APACHE↗