The ICM research agenda on intensive care unit-acquired weakness

We present areas of uncertainty concerning intensive care unit-acquired weakness (ICUAW) and identify areas for future research. Age, pre-ICU functional and cognitive state, concurrent illness, frailty, and health trajectories impact outcomes and should be assessed to stratify patients. In the ICU, early assessment of limb and diaphragm muscle strength and function using nonvolitional tests may be useful, but comparison with established methods of global and specific muscle strength and physical function and determination of their reliability and normal values would be important to advance these techniques. Serial measurements of limb and respiratory muscle strength, and systematic screening for dysphagia, would be helpful to clarify if and how weakness of these muscle groups is independently associated with outcome. ICUAW, delirium, and sedatives and analgesics may interact with each other, amplifying the effects of each individual factor. Reduced mobility in patients with hypoactive delirium needs investigations into dysfunction of central and peripheral nervous system motor pathways. Interventional nutritional studies should include muscle mass, strength, and physical function as outcomes, and prioritize elucidation of mechanisms. At follow-up, ICU survivors may suffer from prolonged muscle weakness and wasting and other physical impairments, as well as fatigue without demonstrable weakness on examination. Further studies should evaluate the prevalence and severity of fatigue in ICU survivors and define its association with psychiatric disorders, pain, cognitive impairment, and axonal loss. Finally, methodological issues, including accounting for baseline status, handling of missing data, and inclusion of patient-centered outcome measures should be addressed in future studies.     

Cognitive screening among acute respiratory failure survivors: a cross-sectional evaluation of the Mini-Mental State Examination

IntroductionThe Mini-Mental State Examination (MMSE) is a common cognitive screening test, but its utility in identifying impairments in survivors of acute respiratory failure is unclear. The purpose of this study was to evaluate MMSE performance versus a concurrently administered detailed neuropsychological test battery in survivors of acute respiratory failure.MethodsThis cross-sectional analysis used data from the ARDSNet Long Term Outcomes Study (ALTOS) and Awakening and Breathing Controlled Trial (ABC). Participants were 242 survivors of acute respiratory failure. The MMSE and detailed neuropsychological tests were administered at 6 and 12 months post-hospital discharge for the ALTOS study, and at hospital discharge, 3 and 12 months for the ABC study. Overall cognitive impairment identified by the MMSE (score <24) was compared to impairments identified by the neuropsychological tests. We also matched orientation, registration, attention, memory and language domains on the MMSE to the corresponding neuropsychological test. Pairwise correlations, sensitivity, specificity, positive and negative predictive values, and agreement were assessed.ResultsAgreement between MMSE and neuropsychological tests for overall cognitive impairment was fair (42 to 80%). Specificity was excellent (≥93%), but sensitivity was poor (19 to 37%). Correlations between MMSE domains and corresponding neuropsychological tests were weak to moderate (6 months: r = 0.11 to 0.28; 12 months: r = 0.09 to 0.34). The highest correlation between the MMSE and neuropsychological domains was for attention at 6 months (r = 0.28) and language at 12 months (r = 0.34).ConclusionsIn acute respiratory failure survivors, the MMSE has poor sensitivity in detecting cognitive impairment compared with concurrently administered detailed neuropsychological tests. MMSE results in this population should be interpreted with caution.     

Charting the Course of Pediatric Nursing Research: The SPN Delphi Study

In order to inform the care of children at this pivotal time in the history of healthcare, the Society of Pediatric Nurses (SPN) sought to identify priorities for nursing research and key challenges facing pediatric nursing. A three round Delphi study was conducted electronically with SPN members. The top 10 priorities and challenges were identified and will serve as a valuable guide for pediatric nursing practice, education, policy and administration over the coming decade.     

Homeostatic cell-cycle control by BLyS: Induction of cell-cycle entry but not G1/S transition in opposition to p18INK4c and p27Kip1

Cell-cycle entry is critical for homeostatic control in physiologic response of higher organisms but is not well understood. The antibody response begins with induction of naive mature B cells, which are naturally arrested in G(0)/G(1) phase of the cell cycle, to enter the cell cycle in response to antigen and cytokine. BLyS (BAFF), a cytokine essential for mature B cell development and survival, is thought to act mainly by attenuation of apoptosis. Here, we show that BLyS alone induces cell-cycle entry and early G(1) cell-cycle progression, but not S-phase entry, in opposition to the cyclin-dependent kinase inhibitors p18(INK4c). Independent of its survival function, BLyS enhances the synthesis of cyclin D2, in part through activation of NF-kappaB, as well as CDK4 and retinoblastoma protein phosphorylation. By convergent activation of the same cell-cycle regulators in opposition to p18(INK4c), B cell receptor signaling induces cell-cycle entry and G(1) progression in synergy with BLyS, but also DNA replication. The failure of BLyS to induce S-phase cell-cycle entry lies in its inability to increase cyclin E and reduce p27(Kip1) expression. Antagonistic cell-cycle regulation by BLyS and p18(INK4c) is functionally linked to apoptotic control and conserved from B cell activation in vitro to antibody response in vivo, further indicating a physiologic role in homeostasis.     

Chronic monoarthritis and previous history of cancer: think about synovial metastasis

Synovial metastases are rare events. Only 37 cases diagnosed by synovial fluid cytologic examination and/or by microscopic investigation of synovial biopsies have been previously reported in the literature. We report another case of shoulder chronic arthritis due to a recurrence of rectal adenocarcinoma and review previous published observations. Generally, this condition carries a poor prognosis with average patients survival of less than 5 months. The possibility of metastatic disease should be considered when an elderly person or patient with a history of previous malignancy presents with a chronic arthritis.     

Validity of a novel computerized cognitive battery for mild cognitive impairment

Background

The NeuroTrax Mindstreams computerized cognitive assessment system was designed for widespread clinical and research use in detecting mild cognitive impairment (MCI). However, the capability of Mindstreams tests to discriminate elderly with MCI from those who are cognitively healthy has yet to be evaluated. Moreover, the comparability between these tests and traditional neuropsychological tests in detecting MCI has not been examined.

Methods

A 2-center study was designed to assess discriminant validity of tests in the Mindstreams Mild Impairment Battery. Participants were 30 individuals diagnosed with MCI, 29 with mild Alzheimer's disease (AD), and 39 healthy elderly. Testing was with the Mindstreams battery and traditional neuropsychological tests. Receiver operating characteristic (ROC) analysis was used to examine the ability of Mindstreams and traditional measures to discriminate those with MCI from cognitively healthy elderly. Between-group comparisons were made (Mann-Whitney U test) between MCI and healthy elderly and between MCI and mild AD groups.

Results

Mindstreams outcome parameters across multiple cognitive domains significantly discriminated among MCI and healthy elderly with considerable effect sizes (p < 0.05). Measures of memory, executive function, visual spatial skills, and verbal fluency discriminated best, and discriminability was at least comparable to that of traditional neuropsychological tests in these domains.

Conclusions

Mindstreams tests are effective in detecting MCI, providing a comprehensive profile of cognitive function. Further, the enhanced precision and ease of use of these computerized tests make the NeuroTrax system a valuable clinical tool in the identification of elderly at high risk for dementia.

     

Associations of markers of inflammation and coagulation with delirium during critical illness

Purpose

To assess the associations between a?priori-selected markers of inflammation and coagulation and delirium during critical illness.

Methods

In this prospective cohort study, we collected blood from mechanically ventilated medical intensive care unit (ICU) patients and measured nine plasma markers of inflammation and coagulation. We assessed patients daily for delirium using the Confusion Assessment Method for the ICU and used multivariable regression to analyze the associations between plasma markers and subsequent delirium, after adjusting for age, severity of illness, and sepsis.

Results

Among the 138 patients studied, with median age of 66?years and median Acute Physiology and Chronic Health Evaluation (APACHE)?II of 27, 107 (78?%) were delirious at some point during the study. Two markers of inflammation and one of coagulation were significantly associated with delirium. After adjusting for covariates, lower plasma concentrations of matrix metalloproteinase-9 (MMP-9) and protein?C were associated with increased probability of delirium (p?=?0.04 and 0.01, respectively), and higher concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1) were associated with increased probability of delirium (p?<?0.01). Concentrations of C-reactive protein (p?=?0.82), myeloperoxidase (p?=?0.11), neutrophil gelatinase-associated lipocalin (p?=?0.70), D-dimer (p?=?0.83), plasminogen activator inhibitor type?1 (p?=?0.98), and Von Willebrand factor antigen (p?=?0.65) were not associated with delirium.

Conclusions

In this study, MMP-9, protein?C, and sTNFR1 were independently associated with subsequent ICU delirium. These results suggest that specific aspects of inflammation and coagulation may play a role in the evolution of delirium during critical illness and that these markers should be examined in larger studies of ICU patients.     

Systemic lupus erythematosus in the elderly

Onset of the disease above the age of 65?years is unusual. This study was undertaken to determine retrospectively the clinical and laboratory features in SLE patients aged over 65?years. It is a retrospective study about 18 elderly patients with SLE out of 342 diagnosed between 1994 and 2009 in the center of Tunisia. All patients had at least 4 of 11 revised ACR criteria of SLE. The frequency of SLE in the elderly was 5.3%. The median age was 70?years (range 66 and 78?years). The sex ratio F/M was 5. The most frequent clinical signs were anemia (83.3%), arthralgia (55.5%), arthritis (38.9%), and malar rash (33.3%). The proteinuria and the neuropsychiatric troubles were present in 27.8% of cases. The pericarditis was present in 16.7% of cases. Antibodies to double stranded DNA (anti-dsDNA) were detected in 66.7%, anti-nucleosome in 50%, anti-SSA and anti-RNP in 27.8%, anti-Sm in 22%, and anti-SSB in 11%. Elderly patients with SLE exhibit distinct clinical and biological manifestations from the classic form. Thus, greater attention should be given for this particular subgroup of SLE patients to avoid delays in diagnosis or misdiagnosis.