Assessing physical function and activity for survivors of a critical illness: A review of instruments

Background

Functional outcomes and health-related quality of life are important measures for survivors of a critical illness. Studies have demonstrated debilitating physical effects for a significant proportion of surviving patients, particularly those with intensive care unit-acquired weakness. Contemporary practice changes include a focus on the continuum of critical illness, with less sedation and more physical activity including mobility while in ICU, and post-ICU and post-hospitalisation activities to support optimal recovery. How to best assess the physical function of patients at different phases of their recovery and rehabilitation is therefore important.

Purpose

This narrative review paper examined observational and functional assessment instruments used for assessing patients across the in-ICU, post-ICU and post-hospital continuum of critical illness.

Methods

Relevant papers were identified from a search of bibliographic databases and a review of the reference list of selected articles. The clinimetric properties of physical function and HRQOL measures and their relevance and utility in ICU were reported in narrative format.

Findings

The review highlighted many different instruments used to measure function in survivors of ICU including muscle strength testing, functional tests and walk tests, and patient centred outcomes such as health related quality of life. In general, the sensitivity and validity of these instruments for use with survivors of a critical illness has not yet been established.

Conclusion

Based on findings from the review, screening of patients using reliable and valid instruments for ICU patients is recommended to inform both practice and future studies of interventions aimed at improving recovery and rehabilitation.     

Hydrodynamic delivery of human IL-15 cDNA increases murine natural killer cell recovery after syngeneic bone marrow transplantation

Immune deficiency immediately following bone marrow transplantation (BMT) increases susceptibility to opportunistic infections as well as tumor relapse. Natural Killer (NK) cells play important roles in the resistance to virally infected and transformed cells. Interleukin (IL)-15 has been shown to be essential for NK cell development and survival. We administered human (h) IL-15 cDNA (pIL-15) via hydrodynamic delivery to murine recipients undergoing congenic BMT to determine its effects on NK cell reconstitution. Hydrodynamic pIL-15 delivery resulted in high levels of hIL-15 protein in the serum that lasted for several days and then quickly declined. The appearance of hIL-15 was followed by a significant increase of mature donor-derived NK cells within the bone marrow, spleens, and livers of the treated recipients. No accumulation of immature NK cell progenitors was observed. The NK cells from IL-15-treated recipients displayed an activated phenotype and were lytically active toward tumor targets in?vitro to a similar degree as did those cells from recipients treated with control plasmid. This suggests that the predominant effect of IL-15 was a quantitative increase in total NK cell numbers and not qualitative changes in NK cell functions. No toxicities or adverse effects were observed. Studies performed in transplanted mice bearing renal carcinoma tumors demonstrated that this mode of hIL-15 gene delivery resulted in increased antitumor responses. These results support the use of cytokine gene transfer-based regimens as a platform to augment NK cell recovery after BMT.     

Differential perinatal risk factors in children with attention-deficit/hyperactivity disorder by subtype

We compared the attention-deficit/hyperactivity disorder(ADHD) combined subtype (ADHD-C) to the ADHD inattentive subtype (ADHD-I) in terms of genetic, perinatal, and developmental risk factors as well as clinical and neuropsychological characteristics. A total of 147 children diagnosed with ADHD between the ages of 6 and 15 years participated in this study. The parents of the children completed the structured diagnostic interview, the ADHD Rating Scale-IV, the Children’s Behavior Checklist, and structured questionnaires on perinatal risk factors, and the children underwent a neuropsychological test and were genotyped. A total of 502 children without ADHD were recruited from the community as a healthy control group. The ADHD-C children showed more severe externalizing symptoms, showed more deficits in a continuous performance test, and were more likely to have comorbid disorders. Maternal stress during pregnancy, postpartum depression, and changes in the primary caretaker during first 3 years were significantly associated with both ADHD-I and ADHD-C. The ADHD-I group was less likely to have received regular prenatal check-ups and more likely to have had postnatal medical illness than the ADHD-C group. There were no significant differences in the genotype frequencies of the dopamine transporter (DAT1) and the serotonin transporter –linked polymorphic region (5-HTTLPR) polymorphisms between ADHD-I and ADHD-C groups. This study shows that the inattentive subtype of ADHD is different from the combined subtype in many parameters including severity of symptoms, comorbidity, neuropsychological characteristics, and environmental risk factors.     

Ex vivo effect of estrogen and progesterone compared with dexamethasone on cell-mediated immunity of HIV-infected and uninfected subjects

To define the effect of estrogen and progesterone concentrations achieved during hormonal contraceptive therapy (HCT) on cell-mediated immunity (CMI) of HIV-infected and uninfected subjects, peripheral blood mononuclear cells (PBMCs) from varicella-zoster virus (VZV)-seropositive individuals were treated with 0.1 ng/mL of estradiol, 33 ng/mL of norgestrel, and 13 ng/mL of dexamethasone and tested for VZV CMI. Estrogen and progesterone decreased VZV lymphocyte proliferation and T helper (Th) 1/inflammatory cytokine secretion, albeit less than dexamethasone. Progesterone decreased the expression of CD69 activation marker on CD8 and CD14 cells and increased the expression of Fas ligand (CD178) on CD14 monocytes, suggesting that induction of apoptosis may contribute to the inhibitory effect of this hormone. Cytokine production of separated CD4, CD8, and CD14 cells confirmed the effect of progesterone on all 3 cellular types, whereas the effect of estrogen was restricted to CD14 monocytes. The estrogen- and progesterone-mediated inhibition of Th1/inflammatory cytokines was greater in HIV-infected subjects (35% decrease for both hormones) compared with uninfected subjects (12% and 19% for estrogen and progesterone, respectively), whereas the effect on proliferation and PBMC phenotype did not differ by HIV status. Overall, HCT concentrations of estrogen and progesterone downregulated ex vivo VZV CMI of HIV-infected and uninfected subjects.     

A pilot study of compositional analysis of the breast and estimation of breast mammographic density using three-dimensional T1-weighted magnetic resonance imaging

PURPOSE: A method and computer tool to estimate percentage magnetic resonance (MR) imaging (MRI) breast density using three-dimensional T(1)-weighted MRI is introduced, and compared with mammographic percentage density [X-ray mammography (XRM)]. MATERIALS AND METHODS: Ethical approval and informed consent were obtained. A method to assess MRI breast density as percentage volume occupied by water-containing tissue on three-dimensional T(1)-weighted MR images is described and applied in a pilot study to 138 subjects who were imaged by both MRI and XRM during the Magnetic Resonance Imaging in Breast Screening study. For comparison, percentage mammographic density was measured from matching XRMs as a ratio of dense to total projection areas scored visually using a 21-point score and measured by applying a two-dimensional interactive program (CUMULUS). The MRI and XRM percent methods were compared, including assessment of left-right and interreader consistency. RESULTS: Percent MRI density correlated strongly (r = 0.78; P < 0.0001) with percent mammographic density estimated using Cumulus. Comparison with visual assessment also showed a strong correlation. The mammographic methods overestimate density compared with MRI volumetric assessment by a factor approaching 2. DISCUSSION: MRI provides direct three-dimensional measurement of the proportion of water-based tissue in the breast. It correlates well with visual and computerized percent mammographic density measurements. This method may have direct application in women having breast cancer screening by breast MRI and may aid in determination of risk.     

Bupropion occupancy of the dopamine transporter is low during clinical treatment

RATIONALE: Bupropion is thought to treat major depression by blocking the dopamine transporter (DAT) because bupropion appears to have a selective affinity for the DAT. The validity of this mechanism has been questioned because the affinity of bupropion for the DAT is quite low. OBJECTIVE: To determine the occupancy of bupropion for the DAT during clinical treatment of patients with depression. METHODS: Positron emission tomography with [(11)C]-RTI32 was used to determine the striatal DAT binding potential (BP) of eight depressed patients before and during treatment with bupropion. BP is proportional to available receptor density (receptors not blocked by drug). Occupancy is the percent change in BP. Eight healthy subjects were similarly studied in a test-retest design. RESULTS: No significant difference in DAT BP was found after bupropion treatment in comparison to the test-retest data. The occupancy after bupropion treatment was 14% (confidence interval 6-22%) as compared to 7% in the test-retest condition. CONCLUSIONS: Bupropion treatment occupies less than 22% of DAT sites. This raises the question as to whether a DAT occupancy of less than 22% is therapeutic or whether there is another mechanism involved during treatment with bupropion.