Measuring and predicting long-term outcomes in older survivors of critical illness.

Older adults (age ≥65 years) now initially survive what were previously fatal critical illnesses, but long-term mortality and disability after critical illness remain high. Most studies show that the majority of deaths among older ICU survivors occur during the first 6 to 12 months after hospital discharge. Less is known about the relationship between critical illness and subsequent cause of death, but longitudinal studies of ICU survivors of pneumonia, stroke, and those who require prolonged mechanical ventilation suggest that many debilitated older ICU survivors die from recurrent infections and sepsis. Recent studies of older ICU survivors have created a new standard for longitudinal critical care outcomes studies with a systematic evaluation of pre-critical illness comorbidities and disability and detailed assessments of physical and cognitive function after hospital discharge. These studies show that after controlling for pre-morbid health, older ICU survivors experience large and persistent declines in cognitive and physical function after critical illness. Long-term health-related quality-of-life studies suggest that some older ICU survivors may accommodate to a degree of physical disability and still report good emotional and social well-being, but these studies are subject to survivorship and proxy-response bias. In order to risk-stratify older ICU survivors for long-term (6-12 months) outcomes, we will need a paradigm shift in the timing and type of predictors measured. Emerging literature suggests that the initial acuity of critical illness will be less important, whereas prehospitalization estimates of disability and frailty, and, in particular, measures of comorbidity, frailty, and disability near the time of hospital discharge will be essential in creating reliable long-term risk-prediction models.

Donor age and early graft failure after lung transplantation: a cohort study.

Lungs from older adult organ donors are often unused because of concerns for increased mortality. We examined associations between donor age and transplant outcomes among 8860 adult lung transplant recipients using Organ Procurement and Transplantation Network and Lung Transplant Outcomes Group data. We used stratified Cox proportional hazard models and generalized linear mixed models to examine associations between donor age and both 1-year graft failure and primary graft dysfunction (PGD). The rate of 1-year graft failure was similar among recipients of lungs from donors age 18-64 years, but severely ill recipients (Lung Allocation Score [LAS] >47.7 or use of mechanical ventilation) of lungs from donors age 56-64 years had increased rates of 1-year graft failure (p-values for interaction = 0.04 and 0.02, respectively). Recipients of lungs from donors <18 and ≥65 years had increased rates of 1-year graft failure (adjusted hazard ratio [HR] 1.23, 95% CI 1.01-1.50 and adjusted HR 2.15, 95% CI 1.47-3.15, respectively). Donor age was not associated with the risk of PGD. In summary, the use of lungs from donors age 56 to 64 years may be safe for adult candidates without a high LAS and the use of lungs from pediatric donors is associated with a small increase in early graft failure.

Hypoalbuminemia and early mortality after lung transplantation: a cohort study.

Hypoalbuminemia predicts disability and mortality in patients with various illnesses and in the elderly. The association between serum albumin concentration at the time of listing for lung transplantation and the rate of death after lung transplantation is unknown. We examined 6808 adults who underwent lung transplantation in the United States between 2000 and 2008. We used Cox proportional hazard models and generalized additive models to examine multivariable-adjusted associations between serum albumin and the rate of death after transplantation. The median follow-up time was 2.7 years. Those with severe (0.5-2.9 g/dL) and mild hypoalbuminemia (3.0-3.6 g/dL) had posttransplant adjusted mortality rate ratios of 1.35 (95% CI: 1.12-1.62) and 1.15 (95% CI: 1.04-1.27), respectively. For each 0.5 g/dL decrease in serum albumin concentration the 1-year and overall mortality rate ratios were 1.48 (95% CI: 1.21-1.81) and 1.26 (95% CI: 1.11-1.43), respectively. The association between hypoalbuminemia and posttransplant mortality was strongest in recipients with cystic fibrosis and interstitial lung disease. Hypoalbuminemia is an independent risk factor for death after lung transplantation.

The type III cytotoxins of Yersinia and Pseudomonas aeruginosa that modulate the actin cytoskeleton.

Initial studies of how bacterial toxins modulate the actin cytoskeleton have focused primarily on the mode of action of these toxins. More recently, studies have addressed the molecular interactions of these toxins with host cell signaling pathways and how toxins modulate cellular physiology. Although each individual toxin has a unique mode of action, general themes have started to emerge between bacterial pathogens. During the course of an infection, many pathogenic bacteria produce toxins that target the actin cytoskeleton and its regulatory proteins. Toxins can either act as positive regulators promoting the assembly of filamentous actin structures or, alternatively, as negative regulators promoting actin filament disassembly. Modulation of the actin cytoskeleton facilitates various infectious processes critical for the success of the pathogen. Intracellular bacteria such as Salmonella typhimurium utilize toxins to promote both assembly and disassembly of the actin cytoskeleton during the infection process. Temporal regulation of toxin activities results in internalization of the bacterium by epithelial cells into specialized vacuoles permissive for growth. In contrast, Yersinia utilizes actin modulating toxins to block internalization by professional antigen-presenting cells such as macrophages and dendritic cells. Modulation of the immune response through the production of actin-regulating toxins appears to be a common approach adopted by several extracellular pathogens. Thus the repertoire of actin-modifying toxins produced by various species is specifically tailored to facilitate the lifestyle of the pathogen. The presence of multiple toxins that modulate the activation state of actin shows the importance of interfering with the cytoskeleton to neutralize the host's innate immune system for the survival and growth of Yersinia and P. aeruginosa.

Tuberculosis and nutrition: disease perceptions and health seeking behavior of household contacts in the Peruvian Amazon.

SETTING: Households of TB patients in the Peruvian Amazon. OBJECTIVE: To investigate how knowledge and beliefs of household contacts about TB affected health seeking behavior. DESIGN: Interviews with 73 patients finishing treatment and 79 of their adult household contacts. RESULTS: Contacts were knowledgeable about free screening and treatment, but contacts who noted weight loss, not cough, were more likely to be screened for TB (P = 0.03). Forty-two per cent reported that TB was prevented by nutrition, 28% by separating eating utensils, and only 19% by avoiding a coughing patient. Only one household contact reported being stigmatized. Stigma centered upon nutrition, and only 12% knew of the association between TB and HIV. Only 14% had a BMI < 20, yet 30% reported regularly going to sleep hungry. Free food packages were reported to be the most important reason for treatment adherence by 33% of patients. CONCLUSION: Contacts misperceived TB as a nutritional disease and did not fear airborne transmission, which should be corrected by public health education. Weight loss, and not cough, led to screening. Stigma appeared to be minimized because risk was perceived as personal, through malnutrition, rather than exposure-based. Nutritional incentives that utilize these beliefs may reduce diagnostic delay and enhance treatment adherence.

Responsibility attributions for men and women giving sane versus crazy explanations for good and bad deeds.

We conducted two studies in which participants evaluated men and women who committed good or bad deeds and afterward gave crazy or sane explanations for their actions. In line with arguments of Thomas Szasz, people were evaluated as more mentally ill, having less intent, and taking little responsibility when they committed deeds that were bad rather than good; those giving crazy explanations for their actions were similarly judged. However, recommended prison sentences did not differ for people who gave crazy or sane explanations for their crimes. Data were integrated into a growing body of research investigating evaluations of criminal responsibility for people with psychological disorders.

Classification and evaluation of the functional results of replanted parts of the hand at the Prince of Wales Hospital and the Prince of Wales Children's Hospital: 1984 to 1988.

This paper describes a simple method of classification and evaluation of the functional results of replanted and revascularized parts in the hand. The results are presented in graphic form and have been analyzed to correlate various factors: injured part, cause, and zone (level) of injury. The type of injury, ischemic time and age have been studied in more detail to determine their influence of the final functional result. The series contains 187 amputated and devascularized parts of the hand in 119 patients who have undergone surgery at the Prince of Wales Hospital from 1984 through 1988. The length of cold or warm ischemic times, up to 16 hours in this series, while not affecting survival of the amputated part, does adversely affect the functional result. The survival rate of replanted parts in children was significantly less favorable than in adults, but the functional results were uniformly superior.

Separation and characterization of cord serum lipoproteins.

Blood was collected from the umbilical cord of infants with a 1-min Apgar score of 9 to 10. Total cord serum lipoproteins were isolated by ultracentrifugation, at a density of 1.220 g/ml. The isolated serum lopoproteins were then separated by gel filtration chromatography on 6% agarose. The overall recovery of the separated lipoprotein cholesterol was 90% or greater. In cord serum, four lipoprotein peaks were found, whereas three peaks were present in adult lipoproteins. The major lipoproteins of cord serum correspond to low density lipoprotein (LDL) and high density lipoprotein (HDL). Very low density lipoproteins (VLDL) were heterogeneous in cord serum. After gel filtration chromatography, the distribution of cord serum cholesterol is about 5% in peak 1, 10% in peak 2, 40% in peak 3 (LDL), and 45% in peak 4 (HDL). An additional difference between the lipoproteins isolated from cord serum and those from adult serum was the slower electrophoretic mobility of cord serum VLDL in agarose gel.