Six-month neuropsychological outcome of medical intensive care unit patients

OBJECTIVE: To examine neuropsychological function, depression, and quality of life 6 months after discharge in patients who received mechanical ventilation in the intensive care unit. DESIGN: Prospective cohort study. SETTING: Tertiary care, medical and coronary intensive care unit of a university-based medical center. STUDY POPULATION: A total of 275 consecutive, mechanically ventilated patients from a medical intensive care unit were prospectively followed. At 6 months, 157 were alive, of whom 41 (26%) returned for extensive follow-up testing. MEASUREMENT AND MAIN RESULTS: Neuropsychological testing and assessment of depression and quality of life were performed at 6-month follow-up. Seven of 41 patients were excluded from further analysis due to preexisting cognitive impairment determined via surrogate interviews using the Modified Blessed Dementia Rating Scale and a review of medical records. On the basis of strict criteria derived from normative data, we found that 11 of 34 patients (32%) were neuropsychologically impaired. Impairment was generally diffuse but occurred primarily in areas of psychomotor speed, visual and working memory, verbal fluency, and visuo-construction. The rate of neuropsychological deficits in the study population was markedly higher than population norms for mild dementia. Scores on the Geriatric Depression Scale-Short Form were significantly more abnormal in the neuropsychologically impaired group than in the nonimpaired group at hospital discharge (p =.04) and at 6-month follow-up (p =.02), and clinically significant depression was found in 27% of impaired subjects at hospital discharge and in 36% at 6-month follow-up. No differences were observed between groups in quality of life as measured with the Short Form Health Survey-12 at discharge or 6-month follow-up. CONCLUSIONS: Prolonged neuropsychological impairment is common among survivors of the medical intensive care unit and occurs with greater than anticipated frequency when compared with relevant normative data. Future investigations are warranted to elucidate the nature of the association between critical illness, neuropsychological impairment, depression, and decreased quality of life.     

Clinical identification of cognitive impairment in ICU survivors: insights for intensivists

Background A growing body of research has demonstrated the presence of ongoing cognitive impairment in large numbers of ICU survivors.Objective This review offers a practical framework for practicing intensivists and those following patients after their ICU stay for the identification of cognitive impairment in ICU survivors.Conclusions Early detection of cognitive impairment in critically ill patients is an important and achievable goal, but overt cognitive impairment remains unrecognized in most cases. However, it can be identified by objective (test scores) or subjective evidence (clinical judgment, patient observation, family interaction).     

A naturally selected dimorphism within the HLA-B44 supertype alters class I structure,peptide repertoire,and T cell recognition

HLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that are both found at a high frequency in all human populations, and yet they only differ by one residue on the alpha2 helix (B*4402 Asp156-->B*4403 Leu156). CTLs discriminate between HLA-B*4402 and B*4403, and these allotypes stimulate strong mutual allogeneic responses reflecting their known barrier to hemopoeitic stem cell transplantation. Although HLA-B*4402 and B*4403 share >95% of their peptide repertoire, B*4403 presents more unique peptides than B*4402, consistent with the stronger T cell alloreactivity observed toward B*4403 compared with B*4402. Crystal structures of B*4402 and B*4403 show how the polymorphism at position 156 is completely buried and yet alters both the peptide and the heavy chain conformation, relaxing ligand selection by B*4403 compared with B*4402. Thus, the polymorphism between HLA-B*4402 and B*4403 modifies both peptide repertoire and T cell recognition, and is reflected in the paradoxically powerful alloreactivity that occurs across this "minimal" mismatch. The findings suggest that these closely related class I genes are maintained in diverse human populations through their differential impact on the selection of peptide ligands and the T cell repertoire.     

Differential contributions of central and effector memory T cells to recall responses

Although the absolute number of memory CD8+ T cells established in the spleen following antigen encounter remains stable for many years, the relative capacity of these cells to mediate recall responses is not known. Here we used a dual adoptive transfer approach to demonstrate a progressive increase in the quality of memory T cell pools in terms of their ability to proliferate and accumulate at effector sites in response to secondary pathogen challenge. This temporal increase in efficacy occurred in CD62L lo (effector memory) and CD62L hi (central memory) subpopulations, but was most prominent in the CD62L hi subpopulation. These data indicate that the contribution of effector memory and central memory T cells to the recall response changes substantially over time.     

Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients

OBJECTIVE: To test for an association between apolipoprotein E (APOE) genotypes and duration of intensive care unit delirium. DESIGN: Prospective, observational cohort study. SETTING: A 541-bed, community-based teaching hospital. PATIENTS: Fifty-three mechanically ventilated intensive care unit patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were managed with standardized sedation and ventilator weaning protocols as part of an ongoing clinical trial and were evaluated prospectively for delirium with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). DNA was extracted from whole blood samples obtained on enrollment, and APOE genotype was determined using polymerase chain reaction followed by restriction enzyme digestion by investigators blinded to the clinical information. Delirium occurred in 47 (89%) patients at some point during the intensive care unit stay. Of the 53 patients, 12 (23%) had an APOE4 allele (APOE4+) and 41 (77%) had only APOE2 or APOE3 alleles (APOE4-). APOE4+ patients were younger (53.2 +/- 21.9 vs. 65.4 +/- 13.4, p = .08) and less often admitted for pneumonia (0% vs. 29.3%, p = .05) compared with APOE4- patients, yet they had a duration of delirium that was twice as long: median (interquartile range), 4 (3, 4.5) vs. 2 (1, 4) days (p = .05). No other clinical outcomes were significantly different between the APOE4+ and APOE4- patients. Using multivariable regression analysis to adjust for age, admission diagnosis of sepsis or acute respiratory distress syndrome or pneumonia, severity of illness, and duration of coma, the presence of APOE4 allele was the strongest predictor of delirium duration (odds ratio, 7.32; 95% confidence interval, 1.82-29.51, p = .005). CONCLUSIONS: APOE4 allele represents the first demonstrated genetic predisposition to longer duration of delirium in humans.     

Characteristics of pain managed at home in children and adolescents with sickle cell disease by using diary self-reports

Pain can begin in the first year of life for individuals with sickle cell disease (SCD) and continue in an unpredictably recurrent manner throughout their life span. Sickle vaso-occlusive pain (sickle pain) can also occur simultaneously with pain of other origins, complicating both assessment and management. Aims of this research were to describe the reliability and validity of a daily diary for data collection with children and adolescents with SCD and to describe characteristics of vaso-occlusive sickle pain episodes (VOE) and other pain reported by children and adolescents with SCD along with home pain management strategies. Thirty-nine children and adolescents (mean age, 10.9 +/- 3.6 years) completed diaries twice daily at home for up to 3 years (mean, 417.9 +/- 272.2 diary days) with excellent compliance. Sickle pain alone was reported on 8.4% of days (n = 1515 days), whereas other pain occurred on 2.7% of days (n = 490) and both sickle pain and other pain on 5.7% (n = 1041 days). Other pain only episodes were shorter and involved fewer sites than sickle pain only episodes. Sickle pain occurred in the extremities and hips, whereas most other pain occurred in the head-neck area. Analgesic medication was taken on 85% of days of sickle pain, whereas analgesics were taken on only 60% of days with other pain. The diary used in this study is a valid and reliable self-report tool. The use of home diaries will improve the understanding of sickle pain and its management and assist in identifying other pain syndromes that may require alternative management.     

Judo Practice in Early Age Promotes High Level of Bone Mass Acquisition of Growing Boys' Skeleton

The current study aimed to exhibit effects of judo training for at least 2 yr on bone mass parameters in growing boys. Our population was composed of one hundred and thirty boys in tanner stage 1 and aged 10.52 ± 0.86 yr. Eleven judo players were therefore, excluded from the study because they do not have participate regularly to the judo training sessions during the last 2 yr. The resting sample was divided into two groups: 50 judo players (JU group) and 69 controls (C group). Bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) were evaluated by using dual-photon X-ray absorptiometry on weight-bearing sites: the whole body, lumbar spine (L2-L4), legs, femoral necks and hips and on the non-weight bearing sites: arms and radiuses. Our findings displayed that judo participation was markedly associated with greater values of bone mass parameters in young judo players than control group. Accordingly, the BMD and BA results exhibited significant differences in the whole body, legs, dominant total hip, arms and both whole radiuses in addition to the dominant femoral neck, the non-dominant total hip and except the non-dominant whole radius for the BMC parameter. Additionally, data of the subject within t test has shown significant differences of bone mass parameters only in the non weight-bearing sites in the judo players without any obvious variation in the controls. Differences of BMD observed on the dominant arm and whole radius in addition to the increased BMC values showed in the dominant whole radius compared with their contra-lateral sites in judo players without any marked variation of BA parameters in all sites in both groups. In growing boys, judo practice was obviously associated with osteogenic effects in specific sites.     

Risk factors for post-traumatic stress disorder symptoms following critical illness requiring mechanical ventilation: a prospective cohort study

Introduction  

Post-traumatic stress disorder (PTSD) has been identified in a significant portion of intensive care unit (ICU) survivors. We sought to identify factors associated with PTSD symptoms in patients following critical illness requiring mechanical ventilation.     

Short-term outcomes in older intensive care unit patients with dementia

OBJECTIVE: To determine the impact of dementia on the outcomes of intensive care unit (ICU) care and use of ICU interventions among older patients. DESIGN: Prospective observational cohort study. SETTING: Urban university teaching hospital. PATIENTS: Patients were 395 patients age >/=65 consecutively admitted to a medical ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Dementia was determined by a previously validated proxy measure, the Modified Blessed Dementia Rating Scale. We chose cut points to focus on patients with moderate-severe dementia at baseline. Our primary outcomes included length of mechanical ventilation and ICU and hospital length of stay. Secondary outcomes included ICU readmission, changes in code status, discharge location, mortality, and use of ICU interventions. Medical record abstraction was performed to determine the rates of ICU outcomes, use of ICU interventions, and potential confounders. Our study documented a prevalence of moderate-severe dementia of 17% in patients age >/=65 admitted to the ICU. Patients with dementia were significantly older (80 vs. 76), more likely to be female (65% vs. 52%), and more likely to be admitted from a nursing home (46% vs. 11%). Patients with dementia had significantly higher Acute Physiology and Chronic Health Evaluation II scores on admission to the ICU (25 vs. 23). Patients with dementia were more likely to have their code status changed to less aggressive in the ICU (24% vs. 14%). There was no significant difference in readmission to the ICU, discharge location, ICU or hospital mortality rate, or use of ICU interventions between patients with and without dementia. CONCLUSIONS: Our study documents no difference in outcomes from ICU care in older patients with and without dementia. There was no increased short-term mortality rate in older patients with dementia compared with those without dementia after admission to the ICU. Presumptions that outcomes from critical care are less favorable in patients with dementia should not drive treatment decisions in the ICU.     

Cellular immune responses of healthy individuals to intradermal administration of an E1-E3- adenovirus gene transfer vector

In animals, Ad-mediated gene transfer initiates anti-Ad host immune responses that vary, depending on vector design, dose, host, and transgene. To begin to understand whether the anti-Ad vector responses in humans simulate those in animals, Ad(GV)CD.10, an E1-E3- Ad5 vector encoding the E. coli cytosine deaminase gene, was administered by the intradermal route to six normal individuals (8 x 10(7) to 8 x 10(9) particle units, each dose administered to two sites; n = 2 per group). No adverse events were observed. Polymerase chain reaction/Southern analysis demonstrated vector genome in the skin through 28 days in all individuals except one of two at the lowest dose. Local induration, independent of vector dose and baseline systemic anti-Ad5 neutralizing antibodies, developed in all subjects (6 to 17 mm, peak by day 3). Biopsies revealed a mild to moderate T cell (CD3+, CD4+, CD8+), B cell, and macrophage infiltrate at day 3, all decreased by day 28. Langerhans cells accumulated primarily in the papillary dermis. The day 3 cellular response was dose independent. On day 28, CD4+ and CD8+ T lymphocytes and macrophages showed dose dependency. There was minimal systemic Ad5-specific lymphocyte proliferation induced by Ad vector administration in three individuals studied, and no Ad5-specific cytotoxic T lymphocytes (evaluated in two subjects) could be detected. Thus, intradermal administration of an E1-E3- Ad vector to normal subjects induces mild/moderate local cellular responses, even in Ad-immunized individuals. These observations provide a baseline to determine if these human anti-Ad vector host responses can be circumvented by using "stealth" vectors and/or immunosuppression.