Neurointensive care; impaired cerebral autoregulation in infants and young children early after inflicted traumatic brain injury: a preliminary report

The objective of this report is to describe cerebral autoregulation after severe inflicted pediatric traumatic brain injury (iTBI). We examined cerebral autoregulation of both cerebral hemispheres (mean autoregulatory index; ARI) in children <5 years with Glasgow Coma Scale (GCS) score of <9 and no evidence of brain death within the first 48 h of pediatric intensive care unit (PICU) admission. Discharge and 6-month Glasgow Outcome Scale (GOS) scores were collected. GOS of <4 reflected poor outcome. All three iTBI and all seven noninflicted TBI (nTBI) patients had admission GCS score of <9. Eight of 10 patients had Autoregulatory Index (ARI) of <0.4 (impaired cerebral autoregulation) of at least one hemisphere. All children with iTBI had poor outcome, and none had intact cerebral autoregulation in both hemispheres. Children with nTBI had better overall outcome than those with iTBI. Two of the children with nTBI had intact autoregulation in both hemispheres and good outcome. Two of the three children with iTBI had differential effects on autoregulation between hemispheres despite bilateral injury. These are, to our knowledge, the first data on cerebral blood flow autoregulation in the unique setting of iTBI and provide a rationale for further study of their relationship to outcome and effects of therapy.     

Nursing Home Resident Outcomes from the Res-Care Intervention

OBJECTIVES: To test the effectiveness of a restorative care (Res-Care) intervention on function, muscle strength, contractures, and quality of life of nursing home residents, with secondary aims focused on strengthening self-efficacy and outcome expectations.
DESIGN: A randomized controlled repeated-measure design was used, and generalized estimating equations were used to evaluate status at baseline and 4 and 12 months after initiation of the Res-Care intervention.
SETTING: Twelve nursing homes in Maryland.
PARTICIPANTS: Four hundred eighty-seven residents consented and were eligible: 256 from treatment sites and 231 from control sites. The majority were female (389, 80.1%) and white (325, 66.8%); 85 (17.4%) were married and the remaining widowed, single, or divorced/separated. Mean age was 83.8 ± 8.2, and mean Mini-Mental State Examination score was 20.4 ± 5.3.
INTERVENTION: Res-Care was a two-tiered self-efficacy-based intervention focused on motivating nursing assistants and residents to engage in functional and physical activities.
MEASUREMENTS: Barthel Index, Tinetti Gait and Balance, grip strength, Dementia Quality-of-Life Scale, self-efficacy, and Outcome Expectations Scales for Function.
RESULTS: Significant treatment-by-time interactions ( P <.05) were found for the Tinetti Mobility Score and its gait and balance subscores and for walking, bathing, and stair climbing.
CONCLUSION: The findings provide some evidence for the utility and safety of a Res-Care intervention in terms of improving function in NH residents.     

Silent infarcts in young children with sickle cell disease

Silent infarcts have been reported most commonly in school-aged children with homozygous sickle cell disease (SCD-SS) and are associated with neurocognitive deficits. However, the prevalence of silent infarcts in younger children with SCD-SS is not well defined. In this retrospective study, brain magnetic resonance imaging and angiography (MRI/A) studies performed before 6 years of age in a cohort of children with SCD-SS were analysed and the prevalence of abnormalities was calculated. Clinical and laboratory parameters were compared between the groups with and without silent infarcts. Sixty-eight of 96 children in the cohort had brain MRI/A performed prior to age 6 years. Of the 65 who were neurologically asymptomatic, 18 (27·7%, 95% CI 17·3–40·2%) had silent infarcts (mean age 3·7 ± 1·1 years, range 1·3–5·9 years). Factors associated with silent infarcts included cerebral vessel stensosis by magnetic resonance angiography, lower rates of vaso-occlusive pain and acute chest syndrome and lower haemoglobin levels. The prevalence of silent infarcts in young children with SCD-SS is similar to that of older children and anaemia and severe vasculopathy may be risk factors.     

Prebreeding maternal immunostimulation with Freund's complete adjuvant reduces placental damage and distal limb defects caused by methylnitrosourea

PROBLEM: Immunostimulation reduces murine teratogen-induced birth defects. It is unclear if placental improvement contributes to this outcome. The current study examined murine placental ultrastructure and fetal limb development following maternal methylnitrosourea (MNU) exposure, +/-Freund's complete adjuvant (FCA) immunostimulation. METHOD OF STUDY: Two murine strains (CD-1, C57BL/6N) were administered MNU on gestation day 9 (GD9), FCA pre-breeding, or FCA + MNU. Fetal limb and placental development were examined on GD14. RESULTS: MNU decreased placental weight and reduced placental cellular viability; FCA reversed these effects. MNU shortened fetal limbs and increased digital defects in both strains. Placentas were less damaged in C57BL/6N versus CD-1 mice, and distal limb malformations improved only in CD-1 mice. FCA immunostimulation also increased pregnancy rate. CONCLUSION: Improved fetal outcome from immune-stimulated mice may not be dependent on improved placental morphology. However, placental function and morphology in immune-stimulated mice may not directly correlate, thus functional improvements should be examined for possible relationship to reduced birth defects.     

Differential gene expression identifies subgroups of renal cell carcinoma

Clear cell carcinoma of the kidney, the most common subtype of renal cell cancer, displays different biological behavior in different patients. This heterogeneity cannot be recognized by light microscopy. In this study, gene expression in 16 clear cell renal cell carcinoma samples and 17 non-malignant tissue types comprising 539 samples was determined using oligonucleotide microarrays representing approximately 40,000 known genes and ESTs. Differences in gene expression were quantified as the fold change in gene expression between the various sets of samples. A set of genes was identified that was overexpressed in the renal cell carcinoma samples compared with the normal kidney samples. Principle component analysis of the set of renal cell carcinomas using this set of genes overexpressed in renal cell cancer revealed the existence of 2 major subgroups among the renal carcinomas. A series of principle component analyses of the set of renal cell carcinomas using different gene sets composed of genes involved in different metabolic pathways also revealed the same 2 major subgroups of the renal cell cancers. Eisen clustering using the same genes also revealed the same 2 major renal cell cancer subsets. Review of the pathology suggested that these 2 subgroups differed in pathologic grade. Genes differentially expressed between the 2 renal cell cancer subsets were identified. Examination of gene expression in each renal cell cancer subset and the pool of renal cell carcinoma samples compared with that in 17 different normal tissues revealed genes specifically overexpressed in renal cell cancer compared with these normal tissues. The authors conclude that gene expression patterns may be useful in helping to further classify subtypes of renal cell carcinoma that may have clinical significance. In addition, the genes identified as overexpressed in each set of clear cell renal cell carcinomas compared with normal tissues may represent useful targets for therapy.     

Intensive care unit length of stay: Benchmarking based on Acute Physiology and Chronic Health Evaluation (APACHE) IV

OBJECTIVE: To revise and update the Acute Physiology and Chronic Health Evaluation (APACHE) model for predicting intensive care unit (ICU) length of stay. DESIGN: Observational cohort study. SETTING: One hundred and four ICUs in 45 U.S. hospitals. PATIENTS: Patients included 131,618 consecutive ICU admissions during 2002 and 2003, of which 116,209 met inclusion criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The APACHE IV model for predicting ICU length of stay was developed using ICU day 1 patient data and a multivariate linear regression procedure to estimate the precise ICU stay for randomly selected patients who comprised 60% of the database. New variables were added to the previous APACHE III model, and advanced statistical modeling techniques were used. Accuracy was assessed by comparing mean observed and mean predicted ICU stay for the excluded 40% of patients. Aggregate mean observed ICU stay was 3.86 days and mean predicted 3.78 days (p < .001), a difference of 1.9 hrs. For 108 (93%) of 116 diagnoses, there was no significant difference between mean observed and mean predicted ICU stay. The model accounted for 21.5% of the variation in ICU stay across individual patients and 62% across ICUs. Correspondence between mean observed and mean predicted length of stay was reduced for patients with a short (< or =1.7 days) or long (> or =9.4 days) ICU stay and a low (<20%) or high (>80%) risk of death on ICU day 1. CONCLUSIONS: The APACHE IV model provides clinically useful ICU length of stay predictions for critically ill patient groups, but its accuracy and utility are limited for individual patients. APACHE IV benchmarks for ICU stay are useful for assessing the efficiency of unit throughput and support examination of structural, managerial, and patient factors that affect ICU stay.     

Is Hospice Associated with Improved End‐of‐Life Care in Nursing Homes and Assisted Living Facilities?

OBJECTIVES: To examine whether hospice enrollment for nursing home (NH) and residential care/assisted living (RC/AL) residents near the end of life is associated with symptoms and symptom management, personal care, spiritual support, and family satisfaction. DESIGN: Structured, retrospective telephone interviews with family and staff who attended to NH and RC/AL residents in the last month of life. SETTING: A stratified sample of 26 NH and 55 RC/AL facilities in four states. Participants: Family members (n=97) and long-term care (LTC) staff (n=104) identified as most involved in care of 124 residents who died over a 15-month period. MEASUREMENTS: A variety of reported measures of care and symptoms before death, including the Discomfort Scale for Dementia of the Alzheimer's Type. RESULTS: Of 124 decedents, 27 (22%) received hospice services. Dementia was less common in hospice enrollees than in decedents who did not receive hospice care. Hospice enrollees more often had moderate/severe pain and dyspnea and received pain treatment and were more likely to receive assistance with mouth care and eating and drinking. There were no differences related to unmet need, and observed differences were largely eliminated when comparisons were limited to residents whose deaths were expected. CONCLUSION: Rates of hospice use observed in this study (22%) were considerably higher than previously reported, although persons with dementia may continue to be underreferred. Hospice use is targeted to dying residents with higher levels of reported pain and dyspnea. Because difference in care largely disappears in cases when death was expected, LTC staff seem to be well positioned to provide end-of-life care for their residents and are advised to remain sensitive to instances in which death may be expected.     

Diagnosing infection levels of four human malaria parasite species by a polymerase chain reaction/ligase detection reaction fluorescent microsphere-based assay

Improving strategies for diagnosing infection by the four human Plasmodium species parasites is important as field-based epidemiologic and clinical studies focused on malaria become more ambitious. Expectations for malaria diagnostic assays include rapid processing with minimal expertise, very high specificity and sensitivity, and quantitative evaluation of parasitemia to be delivered at a very low cost. Toward fulfilling many of these expectations, we have developed a post-polymerase chain reaction (PCR)/ligase detection reaction-fluorescent microsphere assay (LDR-FMA). This assay, which uses Luminex FlexMAP microspheres, provides simultaneous, semi-quantitative detection of infection by all four human malaria parasite species at a sensitivity and specificity equal to other PCR-based assays. In blinded studies using P. falciparum-infected blood from in vitro cultures, we identified infected and uninfected samples with 100% concordance. Additionally, in analyses of P. falciparum in vitro cultures and P. vivax-infected monkeys, comparisons between parasitemia and LDR-FMA signal intensity showed very strong positive correlations (r > 0.95). Application of this multiplex Plasmodium species LDR-FMA diagnostic assay will increase the speed, accuracy, and reliability of diagnosing human Plasmodium species infections in epidemiologic studies of complex malaria-endemic settings.